bluuebunny/crossref_metadata_2025 huggingface dataset:
Small-scale release of non-gene drive mosquitoes in Burkina Faso: from engagement implementation to assessment, a learning journey
Authors: Pare Toe Lea , Barry Nourou , Ky Anselme D. , Kekele Souleymane , Meda Wilfrid , Bayala Korotimi , Drabo Mouhamed , Thizy Delphine , Diabate Abdoulaye
Published: October 2021

Background

Innovative tools are needed to complement the existing approach for malaria elimination. Gene drive mosquitoes are one potential new technology in the control of malaria vectors. Target Malaria is one of the research projects developing this technology, and in July 2019, the project proceeded to an important step for this evaluation pathway: the small-scale release of non-gene drive sterile male mosquitoes in a village in Burkina Faso. In addition to the entomological and laboratory work to prepare for this important milestone, significant community and stakeholder engagement work was done. The existing guidelines on gene drive mosquito provide an overall framework for such engagement work. However, they do not provide a road map on how to proceed or what benchmarks should be used to assess this work.

Methods

This study provides a review of engagement activities relevant to field trials on non-gene drive genetically-modified mosquitoes as well as an assessment framework—using both qualitative and quantitative studies as well as an audit procedure. The latter was implemented to evaluate whether the release activities could proceed with the appropriate level of agreement from the community.

Results

This paper shows the importance of this first phase of work to innovate and learn about engagement processes for responsible research in the field of genetic approaches for malaria vector control. The function of these assessments is crucial for the learning agenda. The assessments demonstrated ways to increase understanding and ensure effective progress with field studies and, therefore, the pathway for responsible research.

Conclusion

Gene drive technology is increasingly considered as a promising approach to control vector borne diseases, in particular malaria. Stakeholders’ involvement in this research process is one of the recurring requirements in international guidance documents. With this paper Target Malaria offers an opportunity to explore the practical achievements and challenges of stakeholder engagement during early phases of a technology evaluation, and in particular how it implemented an assessment framework to learn from its experience.
Intensive surveillance, rapid response and border collaboration for malaria elimination: China Yunnan’s ‘‘3 + 1’’strategy
Authors: Xu Jian-Wei , Lin Zu-Rui , Zhou Yao-Wu , Lee Rogan , Shen Hai-Mo , Sun Xiao-Dong , Chen Qi-Yan , Duan Kai-Xia , Tian Peng , Ding Chun-Li , Xu Shi-Yan , Liu Hui , Zhou Hong-Ning
Published: October 2021

Background

Eliminating malaria and preventing re-establishment of malaria transmission in border areas requires universal coverage of malaria surveillance and a rapid response to any threats (i.e. malaria cues) of re-establishing transmission.

Main text

Strategy 1: Intensive interventions within 2.5 km-wide perimeter along the border to prevent border-spill malaria. The area within 2.5 km along the international border is the travel radius of anopheline mosquitoes. Comprehensive interventions should include: (1) proactive and passive case detection, (2) intensive vector surveillance, (3) evidence-based vector control, and (4) evidence-based preventative treatment with anti-malarial drugs. Strategy 2: Community-based malaria detection and screening of migrants and travellers in frontier townships. Un-permitted travellers cross borders frequently and present in frontier townships. Maintenance of intensified malaria surveillance should include: (1) passive malaria detection in the township hospitals, (2) seek assistance from villager leaders and health workers to monitor cross border travellers, and refer febrile patients to the township hospitals and (3) the county’s Centre for Disease Control and Prevention maintain regular proactive case detection. Strategy 3: Universal coverage of malaria surveillance to detect malaria cues. Passive detection should be consolidated into the normal health service. Health services personnel should remain vigilant to ensure universal coverage of malaria detection and react promptly to any malaria cues. Strategy + 1: Strong collaborative support with neighbouring countries. Based on the agreement between the two countries, integrated control strategies should be carried out to reduce malaria burden for both countries. There should be a clear focus on the border areas between neighbouring countries.

Conclusion

The 3 + 1 strategy is an experience summary of border malaria control and elimination, and then contributed to malaria elimination in Yunnan’s border areas, China. Nevertheless, Yunnan still has remaining challenges of re-establishment of malaria transmission in the border areas, and the 3 + 1 strategy should still be carried out.
Identifying opportunities to engage communities with social mobilisation activities to tackle NCDs in El Salvador in the context of the global COVID-19 pandemic
Authors: Caperon Lizzie , Arakelyan Stella , Innocenti Cinzia , Ager Alastair
Published: October 2021

Background

Social mobilisation is potentially a key tool in the prevention of non-communicable diseases (NCDs) in fragile settings. This formative study addressed existing and potential social mobilisation mechanisms seeking behaviour to tackle NCDs in El Salvador, with an emphasis on the implications in the context of the current COVID-19 pandemic.

Methods

We conducted 19 semi-structured interviews with health workers, government officials, NGO leaders, and community members. Interviews addressed mechanisms for social mobilisation which existed prior to COVID-19, the ways in which these mechanisms tackled NCDs, the impact of COVID-19 on social mobilisation activities and new, emerging mechanisms for social mobilisation in the wake of the COVID-19 pandemic.

Results

Findings indicate a growing awareness of NCDs within communities, with social mobilisation activities seen as valuable in tackling NCDs. However, major barriers to NCD prevention and treatment provision remain, with COVID-19 constraining many possible social mobilisation activities, leaving NCD patients with less support. Factors linked with effective social mobilisation of communities for NCD prevention included strong engagement of community health teams within community structures and the delivery of NCD prevention and management messages through community meetings with trusted health professionals or community members. There are gender differences in the experience of NCDs and women were generally more engaged with social mobilisation activities than men. In the context of COVID-19, traditional forms of social mobilisation were challenged, and new, virtual forms emerged. However, these new forms of engagement did not benefit all, especially those in hard-to-reach rural areas. In these contexts, specific traditional forms of mobilisation such as through radio (where possible) and trusted community leaders - became increasingly important.

Conclusions

New mechanisms of fostering social mobilisation include virtual connectors such as mobile phones, which enable mobilisation through platforms such as WhatsApp, Facebook and Twitter. However, traditional forms of social mobilisation hold value for those without access to such technology. Therefore, a combination of new and traditional mechanisms for social mobilisation hold potential for the future development of social mobilisation strategies in El Salvador and, as appropriate, in other fragile health contexts.
Serum lipids are associated with nonalcoholic fatty liver disease: a pilot case-control study in Mexico
Authors: Flores Yvonne N. , Amoon Aryana T. , Su Baolong , Velazquez-Cruz Rafael , Ramírez-Palacios Paula , Salmerón Jorge , Rivera-Paredez Berenice , Sinsheimer Janet S. , Lusis Aldons J. , Huertas-Vazquez Adriana , Saab Sammy , Glenn Beth A. , May Folasade P. , Williams Kevin J. , Bastani Roshan , Bensinger Steven J.
Published: October 2021

Background

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and cirrhosis. NAFLD is mediated by changes in lipid metabolism and known risk factors include obesity, metabolic syndrome, and diabetes. The aim of this study was to better understand differences in the lipid composition of individuals with NAFLD compared to controls, by performing direct infusion lipidomics on serum biospecimens from a cohort study of adults in Mexico.

Methods

A nested case-control study was conducted with a sample of 98 NAFLD cases and 100 healthy controls who are participating in an on-going, longitudinal study in Mexico. NAFLD cases were clinically confirmed using elevated liver enzyme tests and liver ultrasound or liver ultrasound elastography, after excluding alcohol abuse, and 100 controls were identified as having at least two consecutive normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (< 40 U/L) results in a 6-month period, and a normal liver ultrasound elastography result in January 2018. Samples were analyzed on the Sciex Lipidyzer Platform and quantified with normalization to serum volume. As many as 1100 lipid species can be identified using the Lipidyzer targeted multiple-reaction monitoring list. The association between serum lipids and NAFLD was investigated using analysis of covariance, random forest analysis, and by generating receiver operator characteristic (ROC) curves.

Results

NAFLD cases had differences in total amounts of serum cholesterol esters, lysophosphatidylcholines, sphingomyelins, and triacylglycerols (TAGs), however, other lipid subclasses were similar to controls. Analysis of individual TAG species revealed increased incorporation of saturated fatty acyl tails in serum of NAFLD cases. After adjusting for age, sex, body mass index, andPNPLA3genotype, a combined panel of ten lipids predicted case or control status better than an area under the ROC curve of 0.83.

Conclusions

These preliminary results indicate that the serum lipidome differs in patients with NAFLD, compared to healthy controls, and suggest that assessing the desaturation state of TAGs or a specific lipid panel may be useful clinical tools for the diagnosis of NAFLD.
Preprocedural Lp(a) level and ApoB/ApoA-Ι ratio and the risk for contrast-induced acute kidney injury in patients undergoing emergency PCI
Authors: Tao Jun , Dai Wen , Ye Chenglin , Yao Qian , Zhou Man , Li Yan
Published: October 2021

Background

High serum Lipoprotein(a) (Lp(a)) level and Apolipoprotein B/Apolipoprotein AΙ (ApoB/ApoA-Ι) ratio are risk factors for cardiovascular disease and kidney disease and have been found to be correlated with the prevalence and prognosis of various kidney diseases. However, it is not clear whether the serum Lp(a) level and ApoB/ApoA-Ι ratio pre-PCI are correlated with the prevalence of contrast-induced acute kidney injury (CI-AKI).

Methods

A total of 931 participants undergoing emergency PCI from July 2018 to July 2020 were included. According to whether the serum creatinine concentration was higher than the baseline concentration (by ≥25% or ≥ 0.5 mg/dL) 48–72 h after contrast exposure, these participants were divided into a CI-AKI group (n = 174) and a non-CI-AKI group (n = 757). Serum Lp(a), ApoA-Ι and ApoB concentration were detected in the patients when they were admitted to hospital, and the ApoB/ApoA-Ι ratio was calculated. Logistic regression and restricted cubic spline analyses were used to explore the correlation between the Lp(a) concentration or the ApoB/ApoA-Ι ratio and the risk of CI-AKI.

Results

Among the 931 participants undergoing emergency PCI, 174 (18.69%) participants developed CI-AKI. Compared with the non-CI-AKI group, the Lp(a) level and ApoB/ApoA-Ι ratio pre-PCI in the CI-AKI group were significantly higher (P < 0.05). The incidence of CI-AKI was positively associated with the serum Lp(a) level and ApoB/ApoA-Ι ratio pre-PCI in each logistic regression model (P < 0.05). After adjusting for all the risk factors included in this study, restricted cubic spline analyses found that the Lp(a) level and the ApoB/ApoA-Ι ratio before PCI, within certain ranges, were positively associated with the prevalence of CI-AKI.

Conclusion

High Lp(a) levels and high ApoB/ApoA-Ι ratios before PCI are potential risk factors for CI-AKI.
The usefulness of obesity and lipid-related indices to predict the presence of Non-alcoholic fatty liver disease
Authors: Sheng Guotai , Lu Song , Xie Qiyang , Peng Nan , Kuang Maobin , Zou Yang
Published: October 2021

Background

Conicity index, body-shape index, lipid accumulation product (LAP), waist circumference (WC), triglyceride, triglyceride-glucose (TyG) index, hepatic steatosis index (HSI), waist-to-height ratio (WHtR), TyG index-related parameters (TyG-WHtR, TyG-BMI, TyG-WC), body mass index (BMI), visceral adiposity index, triglyceride to high-density lipoprotein cholesterol ratio and body roundness index have been reported as reliable markers of non-alcoholic fatty liver disease (NAFLD). However, there is debate about which of the above obesity and lipid-related indices has the best predictive performance for NAFLD risk.

Methods

This study included 6870 female and 7411 male subjects, and 15 obesity and lipid-related indices were measured and calculated. NAFLD was diagnosed by abdominal ultrasound. The area under the curve (AUC) of 15 obesity and lipid-related indices were calculated by receiver operating characteristic (ROC) analysis.

Results

Among the 15 obesity and lipid-related indices, the TyG index-related parameters had the strongest association with NAFLD. ROC analysis showed that except for ABSI, the other 14 parameters had high predictive value in identifying NAFLD, especially in female and young subjects. Most notably, TyG index-related parameters performed better than other parameters in predicting NAFLD in most populations. In the female population, the AUC of TyG-WC for predicting NAFLD was 0.9045, TyG-BMI was 0.9084, and TyG-WHtR was 0.9071. In the male population, the AUC of TyG-WC was 0.8356, TyG-BMI was 0.8428, and TyG-WHtR was 0.8372. In addition, BMI showed good NAFLD prediction performance in most subgroups (AUC>0.8).

Conclusions

Our data suggest that TyG index-related parameters, LAP, HSI, BMI, and WC appear to be good predictors of NAFLD. Of these parameters, TyG index-related parameters showed the best predictive potential.
Mesoporous polydopamine nanoparticles carrying peptide RL-QN15 show potential for skin wound therapy
Authors: Qin Pan , Meng Yi , Yang Ying , Gou Xinyu , Liu Naixin , Yin Saige , Hu Yan , Sun Huiling , Fu Zhe , Wang Yinglei , Li Xiaojie , Tang Jing , Wang Ying , Deng Ziwei , Yang Xinwang
Published: October 2021

Background

Skin wound healing remains a considerable clinical challenge, thus stressing the urgent need for the development of new interventions to promote repair. Recent researches indicate that both peptides and nanoparticles may be potential therapies for the treatment of skin wounds.

Methods

In the current study, the mesoporous polydopamine (MPDA) nanoparticles were prepared and the peptide RL-QN15 that was previously identified from amphibian skin secretions and exhibited significant potential as a novel prohealing agent was successfully loaded onto the MPDA nanoparticles, which was confirmed by results of analysis of scanning electron microscopy and fourier transform infrared spectroscopy. The encapsulation efficiency and sustained release rate of RL-QN15 from the nanocomposites were determined. The prohealing potency of nanocomposites were evaluated by full-thickness injured wounds in both mice and swine and burn wounds in mice.

Results

Our results indicated that, compared with RL-QN15 alone, the prohealing potency of nanocomposites of MPDA and RL-QN15 in the full-thickness injured wounds and burn wounds in mice was increased by up to 50 times through the slow release of RL-QN15. Moreover, the load on the MPDA obviously increased the prohealing activities of RL-QN15 in full-thickness injured wounds in swine. In addition, the obvious increase in the prohealing potency of nanocomposites of MPDA and RL-QN15 was also proved by the results from histological analysis.

Conclusions

Based on our knowledge, this is the first research to report that the load of MPDA nanoparticles could significantly increase the prohealing potency of peptide and hence highlighted the promising potential of MPDA nanoparticles-carrying peptide RL-QN15 for skin wound therapy.

Graphic abstract
Magnetically guided theranostics: montmorillonite-based iron/platinum nanoparticles for enhancing in situ MRI contrast and hepatocellular carcinoma treatment
Authors: Chan Ming-Hsien , Lu Chih-Ning , Chung Yi-Lung , Chang Yu-Chan , Li Chien-Hsiu , Chen Chi-Long , Wei Da-Hua , Hsiao Michael
Published: October 2021

In Asia, including Taiwan, malignant tumors such as Hepatocellular carcinoma (HCC) one of the liver cancer is the most diagnosed subtype. Magnetic resonance imaging (MRI) has been a typical diagnostic method for accurately diagnosing HCC. When it is difficult to demonstrate non-enhanced MRI of tumors, radiologists can use contrast agents (such as Gd3+, Fe3O4, or FePt) for T1-weighted and T2-weighted imaging remain in the liver for a long time to facilitate diagnosis via MRI. However, it is sometimes difficult for T2-weighted imaging to detect small tumor lesions because the liver tissue may absorb iron ions. This makes early cancer detection a challenging goal. This challenge has prompted current research to create novel nanocomposites for enhancing the noise-to-signal ratio of MRI. To develop a method that can more efficiently diagnose and simultaneously treat HCC during MRI examination, we designed a functionalized montmorillonite (MMT) material with a porous structure to benefit related drugs, such as mitoxantrone (MIT) delivery or as a carrier for the FePt nanoparticles (FePt NPs) to introduce cancer therapy. Multifunctional FePt@MMT can simultaneously visualize HCC by enhancing MRI signals, treating various diseases, and being used as an inducer of magnetic fluid hyperthermia (MFH). After loading the drug MIT, FePt@MMT-MIT provides both MFH treatment and chemotherapy in one nanosystem. These results ultimately prove that functionalized FePt@MMT-MIT could be integrated as a versatile drugs delivery system by combining with MRI, chemotheraeutic drugs, and magnetic guide targeting.
Stroke risk and its association with quality of life: a cross-sectional study among Chinese urban adults
Authors: Yao Huiqing , Zhang Juhua , Wang Yanmei , Wang Qingqing , Zhao Fei , Zhang Peng
Published: October 2021

Background

Stroke is a leading cause of mortality and disability worldwide. Most stroke risk studies focused on more established biological and pathophysiological risk factors such as hypertension and smoking, psychosocial factors such as quality of life are often under-investigated and thus less reported. The current study aims to estimate stroke risk and explore the impact of quality of life on stroke risk among a community sample of urban residents in Shanghai.

Methods

This cross-sectional study was conducted in Fengxian District of Shanghai City from December 2018 to April 2019. 4030 representative participants were recruited through a multistage, stratified, probability proportional to size sampling method and completed the study. Stroke risk was assessed using the Rapid Stroke Risk Screening Chart that included 8 risk factors for stroke. Quality of life was measured using the World Health Organization Quality of Life-brief version (WHOQOL-BREF).

Results

One-third of residents were at risk for stroke, including 14.39% at high risk, and 18.68% at middle risk. The top three most commonly reported risk factors were physical inactivity (37.30%), hypertension (25.38%), and smoking (17.32%). Quality of life and its four domains were all independently and significantly associated with stroke risk. Multinominal logistic regressions showed that a one-unit increase in the quality of life was associated with a decreased relative risk for middle-risk relative to low-risk of stroke by a factor of 0.988 (95% CI:0.979, 0.997, P = 0.007), and a decreased relative risk for high-risk relative to low-risk of stroke by a factor of 0.975 (95% CI:0.966, 0.984, P < 0.001).

Conclusions

Our findings showed an alarmingly high prevalence of stroke risk among the sample, which may require future intervention programs to focus on improving both biological and behavioral risk factors such as increasing physical activity, early diagnosis and treatment of hypertension, and smoking cessation, as well as improving psychosocial factors such as quality of life.
Evaluation of the Oxford Hip Score: Does it still have content validity? Interviews of total hip arthroplasty patients
Authors: Holmenlund Camilla , Overgaard Søren , Bilberg Randi , Varnum Claus
Published: October 2021

Background

The Oxford Hip Score is used to evaluate the outcome after total hip arthroplasty. The Oxford Hip Score was developed more than 20 years ago with only some degree of patient involvement. We question if the Oxford Hip Score is still relevant for the present-day total hip artrhoplasty patients. We aimed to determine whether the Oxford Hip Score contains items that are relevant for present-day patients with osteoarthritis undergoing total hip arthroplasty, thus investigating the content validity.

Methods

Patients aged 60–75 years, undergoing total hip arthroplasty for primary osteoarthritis were recruited to participate in focus group interviews preoperatively and at 3 and 12 months after primary total hip arthroplasty. We conducted 6 focus group interviews in which 30 patients participated. The interviews were audio-recorded and transcribed verbatim. Using Interpretative Phenomenological Analysis, we inductively organised the interview transcripts into particular items/themes which we then compared to items in the Oxford Hip Score.

Results

We identified 6 general items with 41 sub-items. The 6 general items were pain, walking, physical activities, functional abilities, quality of life and psychological health. We found that items in the Oxford Hip Score were all in some way relevant to the patients but that the Oxford Hip Score lacks several important items relevant for present-day total hip artrhoplasty patients, including several physical activities, functional abilities and certain aspects of quality of life and psychological health.

Conclusion

We found that the Oxford Hip Score lacks important items for present-day patients in our population. Due to findings regarding several additional items that are not present in the Oxford Hip Score, particularly concerning physical activities and quality of life, we question the content validity of the Oxford Hip Score for a present-day population. Our findings indicate a need for a revision of the Oxford Hip Score.
Impact of human papillomavirus infection on semen parameters and reproductive outcomes
Authors: Jaworek Hana , Koudelakova Vladimira , Oborna Ivana , Zborilova Blazena , Brezinova Jana , Ruzickova Dagmar , Vrbkova Jana , Kourilova Pavla , Hajduch Marian
Published: October 2021

Background

Human papillomavirus (HPV) has been shown to adversely affect human reproduction. We aimed to evaluate the prevalence of human papillomavirus (HPV) infection in men and its correlation with semen parameters and reproductive outcomes.

Methods

Semen samples and penile swabs were collected from potential sperm donors (SD, n = 97) and male partners of infertile couples (IM, n = 328). The presence of HPV DNA in semen samples and penile swabs was analyzed. Associations between hrHPV positive status and fertility outcomes as well as socio-behavioral and health characteristics were evaluated using the R software package.

Results

High-risk HPV (hrHPV) genotypes were detected in 28.9% of SD and 35.1% of IM (P = 0.312). Penile swabs were more frequently positive for hrHPV genotypes than semen samples in both IM (32.3% vs. 11.9%, P < 0.001) and SD (26.8% vs. 6.2%, P = 0.006).

Men with hrHPV positive semen samples had lower semen volume (median volume 2.5 ml vs. 3 ml, P = 0.009), sperm concentration (median concentration 16 × 106/ml vs. 31 × 106/ml, P = 0.009) and total sperm count (median count 46 × 106 vs. 82 × 106, P = 0.009) than men with hrHPV negative samples. No association was identified between penile hrHPV status and semen parameters.

Conclusions

Our findings indicate that penile HPV infection is common in both potential sperm donors and men from infertile couples. Although HPV positivity is higher in penile swabs, only HPV infection in semen samples affects sperm parameters. However, there was no association between hrHPV positivity in semen and fertility outcomes including abortion rate.
Alterations of miR-16, miR-let-7a and their target genes expression in human blastocysts following vitrification and re-vitrification
Authors: Daneshvar Maryam , Movahedin Mansoureh , Salehi Mohammad , Noruzinia Mehrdad
Published: October 2021

Embryo cryopreservation is a widely used technique in infertility management and today is an essential part of assisted reproductive technology (ART). In some cases, re-vitrification can be applied to good quality supernumerary warmed embryos that have not been transferred in the present cycle. However, there is no study about re-vitrification impact on microRNA and gene expression in human embryos. The purpose of this study is to evaluate miR-16, miR-let7a and target genes expression in in vitro produced human blastocysts following re-vitrification.

Day3 embryos obtained from ICSI cycles of fertile couples referring for family balancing program were biopsied and cultured individually. On the fourth day (post-ICSI) male ones (choices of their parents) were transferred and the females (good quality embryos) were donated for research. Donated embryos were cultured to blastocyst stage and assigned to three groups: fresh, vitrified and re-vitrification. Embryos were vitrified on Cryotech carriers. Then blastocysts of three groups were individually assessed for expression of miR-16, miR-let7a and target genes.

The results showed that re-vitrification of human blastocysts did not affect the ability to re-expand in culture. In addition, significant decrease was observed in miR-16 and miR-let7a expression in re-vitrified group compared to fresh (p < 0.05). A significant upregulation of the target genes ITGβ3 and BCL-2 in re-vitrified and vitrified embryos was observed compared to the fresh group (p < 0.05). The expression of BAX as a pro-apoptotic gene showed a significant decrease in re-vitrification group comparing with the fresh one (P < 0.05).

The results of this research indicated that re-vitrification of embryos changes the expression of miR-16, miR-let-7a and their target genes. These alterations include increased expression of BCl-2 and ITGβ3 genes which play important roles in embryo survival and implantation, respectively. Clinical proof of these effects requires further research.
A systematic review of the profile and density of the maternal and child health workforce in China
Authors: Zhang Huan , Liu Xiaoyun , Penn-Kekana Loveday , Ronsmans Carine
Published: October 2021

Background

To track progress in maternal and child health (MCH), understanding the health workforce is important. This study seeks to systematically review evidence on the profile and density of MCH workers in China.

Methods

We searched 6 English and 2 Chinese databases for studies published between 1 October 1949 and 20 July 2020. We included studies that reported on the level of education or the certification status of all the MCH workers in one or more health facilities and studies reporting the density of MCH workers per 100 000 population or per 1000 births. MCH workers were defined as those who provided MCH services in mainland China and had been trained formally or informally.

Results

Meta-analysis of 35 studies found that only two-thirds of obstetricians and paediatricians (67%, 95% CI: 59.6–74.3%) had a bachelor or higher degree. This proportion was lower in primary-level facilities (28% (1.5–53.9%)). For nurses involved in MCH care the proportions with a bachelor or higher degree were lower (20.0% (12.0–30.0%) in any health facility and 1% (0.0–5.0%) in primary care facilities). Based on 18 studies, the average density of MCH doctors and nurses was 11.8 (95% CI: 7.5–16.2) and 11.4 (7.6–15.2) per 100 000 population, respectively. The average density of obstetricians was 9.0 (7.9–10.2) per 1000 births and that of obstetric nurses 16.0 (14.8–17.2) per 1000 births. The density of MCH workers is much higher than what has been recommended internationally (three doctors and 20 midwives per 3600 births).

Conclusions

Our review suggests that the high density of MCH workers in China is achieved through a mix of workers with high and low educational profiles. Many workers labelled as “obstetricians” or “paediatrician” have lower qualifications than expected. China compensates for these low educational levels through task-shifting, in-service training and supervision.
Cost-effectiveness analysis of a strategy to delay progression to dialysis and death among chronic kidney disease patients in Lima, Peru
Authors: Saldarriaga E. M. , Bravo-Zúñiga J. , Hurtado-Roca Y. , Suarez V.
Published: October 2021

Background

The Renal Health Program (RHP) was implemented in 2013 as a secondary prevention strategy to reduce the incidence of patients initiating dialysis and overall mortality. A previous study found that adherent patients have 58% protection against progression to dialysis compared to non-adherent. The main objective of the study was to estimate the lifetime economic and health consequences of the RHP intervention to determine its cost-effectiveness in comparison with usual care.

Methods

We use a Markov model of three health stages to simulate disease progression among chronic kidney disease patients in Lima, Peru. The simulation time-horizon was 30 years to capture the lifetime cost and health consequences comparing the RHP to usual care. Costs were estimated from the payer perspective using institutional data. Health outcomes included years lived free of dialysis (YL) and quality adjusted life years (QALY). We conducted a probabilistic sensitivity analysis (PSA) to assess the robustness of our estimates against parameter uncertainty.

Results

We found that the RHP was dominant—cost-saving and more effective—compared to usual care. The RHP was 783USD cheaper than the standard of care and created 0.04 additional QALYs, per person. The Incremental Cost-Effectiveness Ratio (ICER) showed a cost per QALY gained of $21,660USD. In the PSA the RHP was dominant in 996 out of 1000 evaluated scenarios.

Conclusions

The RHP was cheaper than the standard of care and more effective due to a reduction in the incidence of patients progressing to dialysis, which is a very expensive treatment and many times inaccessible. We aim these results to help in the decision-making process of scaling-up and investment of similar strategies in Peru. Our results help to increase the evidence in Latin America where there is a lack of information in the long-term consequences of clinical-management-based prevention strategies for CKD patients.
Neural networks and hospital length of stay: an application to support healthcare management with national benchmarks and thresholds
Authors: Ippoliti Roberto , Falavigna Greta , Zanelli Cristian , Bellini Roberta , Numico Gianmauro
Published: October 2021

Background

The problem of correct inpatient scheduling is extremely significant for healthcare management. Extended length of stay can have negative effects on the supply of healthcare treatments, reducing patient accessibility and creating missed opportunities to increase hospital revenues by means of other treatments and additional hospitalizations.

Methods

Adopting available national reference values and focusing on a Department of Internal and Emergency Medicine located in the North-West of Italy, this work assesses prediction models of hospitalizations with length of stay longer than the selected benchmarks and thresholds. The prediction models investigated in this case study are based on Artificial Neural Networks and examine risk factors for prolonged hospitalizations in 2018. With respect current alternative approaches (e.g., logistic models), Artificial Neural Networks give the opportunity to identify whether the model will maximize specificity or sensitivity.

Results

Our sample includes administrative data extracted from the hospital database, collecting information on more than 16,000 hospitalizations between January 2018 and December 2019. Considering the overall department in 2018, 40% of the hospitalizations lasted more than the national average, and almost 3.74% were outliers (i.e., they lasted more than the threshold). According to our results, the adoption of the prediction models in 2019 could reduce the average length of stay by up to 2 days, guaranteeing more than 2000 additional hospitalizations in a year.

Conclusions

The proposed models might represent an effective tool for administrators and medical professionals to predict the outcome of hospital admission and design interventions to improve hospital efficiency and effectiveness.
Bi-directional relationships between physical activity and mental health among a large sample of Canadian youth: a sex-stratified analysis of students in the COMPASS study
Authors: Buchan M. Claire , Romano Isabella , Butler Alexandra , Laxer Rachel E. , Patte Karen A. , Leatherdale Scott T.
Published: October 2021

Objective

The aim of this research was to examine the bidirectional association between self-reported symptoms of mental disorder and physical activity among a large sample of Canadian secondary school students over time.

Methods

Linked survey data were obtained from 28,567 grade 9 to 12 students across Canada participating in two waves of the COMPASS Study (2017–18; 2018–19). Autoregressive cross-lagged models were run to examine the reciprocal relationships between self-reported moderate-to-vigorous physical activity (MVPA) and symptoms of depression (CESD-10) and anxiety (GAD-7). Models were stratified by gender, and accounted for grade, ethno-racial identity, and school-level clustering.

Results

Autoregressive associations show that neither symptoms of anxiety nor depression, at baseline, were predictive of mean MVPA at follow-up – consistent for the full sample and among both males and females. Higher MVPA among males at baseline was associated with lower symptoms of both anxiety (β = − 0.03, p = 0.002) and depression (β = − 0.05, p < 0.001) at follow-up. However, among females, higher MVPA at baseline was associated with greater symptoms of anxiety (β = 0.03, p < 0.001), but not symptoms of depression (β = 0.01, p = 0.073), at follow-up.

Conclusion

In our large sample of Canadian secondary school students, associations between physical activity and symptoms of mental disorder were not bi-directional, and these relationships differed in males and females. This study illustrates the complex nature of the relationship between physical activity and symptoms of mental disorder among youth. While results support the benefits of promoting physical activity among males to prevent or manage internalizing symptoms, the relationship among females warrants further investigation.
Understanding children’s preference for park features that encourage physical activity: an adaptive choice based conjoint analysis
Authors: Veitch Jenny , Ball Kylie , Rivera Elise , Loh Venurs , Deforche Benedicte , Timperio Anna
Published: October 2021

Background

Parks are a key setting for physical activity for children. However, little is known about which park features children prefer and which features are most likely to encourage them to be active in parks. This study examined the relative importance of park features among children for influencing their choice of park for engaging in park-based physical activity.

Methods

Children (n = 252; 8-12 years, 42% male) attending three primary schools in Melbourne, Australia completed a survey at school. They were required to complete a series of Adaptive Choice-Based Conjoint analysis tasks, with responses used to identify the part-worth utilities and relative importance scores of selected park features using Hierarchical Bayes analyses within Sawtooth Software.

Results

For the overall sample and both boys and girls, the most important driver of choice for a park that would encourage them to be active was presence of a flying fox (overall conjoint analysis relative importance score: 15.8%; 95%CI = 14.5, 17.1), followed by a playground (13.5%; 95%CI = 11.9, 15.2). For the overall sample, trees for climbing had the third highest importance score (10.2%; 95%CI = 8.9, 11.6); however, swings had 3rd highest importance for girls (11.1, 95%CI = 9.3, 12.9) and an obstacle course/parkour area had the 3rd highest importance score for boys (10.7, 95%CI = 9.0, 12.4). For features with two levels, part-worth utility scores showed that the presence of a feature was always preferred over the absence of a feature. For features with multiple levels, long flying foxes, large adventure playgrounds, lots of trees for climbing, large round swings, large climbing equipment, and large grassy open space were the preferred levels.

Conclusion

To ensure parks appeal as a setting that encourages children to engage in physical activity, park planners and local authorities and organisations involved in park design should prioritise the inclusion of a long flying fox, large adventure playgrounds, lots of trees for climbing, large round swings and obstacle courses/parkour areas.
Chromosome aneuploidy analysis in embryos derived from in vivo and in vitro matured human oocytes
Authors: Li Jianhua , Chen Jing , Sun Tiecheng , Zhang Shuiwen , Jiao Tingting , Chian Ri-Cheng , Li Youzhu , Xu Ye
Published: October 2021

Background

In vitro oocyte maturation (IVM) is being increasingly approached in assisted reproductive technology (ART). This study aimed to evaluate the quality of embryos generated by in-vitro matured immature follicles, as a guideline for further clinical decision-making.

Methods

A total of 52 couples with normal karyotypes underwent in vitro fertilization, and 162 embryos were donated for genetic screening. Embryos in IVF group were generated by mature follicles retrieved during gonadotrophin-stimulated in vitro fertilization (IVF) cycles. And embryos in IVM group were fertilized from IVM immature oocytes.

Results

The average age of the women was 30.50 ± 4.55 years (range 21–42 years) with 87 embryos from IVF group and 75 embryos from IVM group. The rate of aneuploid with 28 of the 87 (32.2%) embryos from IVF group and 21 of the 75 (28%) embryos from IVM group, with no significant difference. The frequency of aneuploid embryos was lowest in the youngest age and increased gradually with women’s age, whether in IVF group or IVM group and risen significantly over 35 years old. The embryos with morphological grade 1 have the lowest aneuploidy frequency (16.6%), and increase by the grade, especially in IVF group. In grade 3, embryos in IVM group were more likely to be euploid than IVF group (60% vs 40%, respectively).

Conclusions

IVM does not affect the quality of embryos and does not increase the aneuploidy rate of embryos. It is clinically recommended that women more than 35 years have a high aneuploidy rate and recommended to test by PGS (strongly recommended to screened by PGS for women more than 40 years). Women aged less than 35 years old for PGS according to their physical and economic conditions. Embryo with poor quality is also recommended to test by PGS, especially for grade III embryos.
CENPA promotes clear cell renal cell carcinoma progression and metastasis via Wnt/β-catenin signaling pathway
Authors: Wang Qi , Xu Jiaju , Xiong Zhiyong , Xu Tianbo , Liu Jingchong , Liu Yuenan , Chen Jiaping , Shi Jian , Shou Yi , Yue Changjie , Liu Di , Liang Huageng , Yang Hongmei , Yang Xiong , Zhang Xiaoping
Published: October 2021

Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the kidney. New and reliable biomarkers are in urgent need for ccRCC diagnosis and prognosis. The CENP family is overexpressed in many types of cancers, but its functions in ccRCC have not been fully clarified. In this paper, we found that several CENP family members were highly expressed in ccRCC tissues. Also, CENPA expression level was related to clinicopathological grade and prognosis by weighted gene co-expression network analysis (WGCNA). CENPA served as a representative CENP family member as a ccRCC biomarker. Further in vitro experiments verified that overexpression of CENPA promoted ccRCC proliferation and metastasis by accelerating the cell cycle and activating the Wnt/β-catenin signaling pathway. The elevated β-catenin led by CENPA overexpression translocated to nucleus for downstream effect. Functional recovery experiment confirmed that Wnt/β-catenin pathway was essential for ccRCC progression and metastasis. Developing selective drugs targeting CENPA may be a promising direction for cancer treatment.
Integrative eQTL-weighted hierarchical Cox models for SNP-set based time-to-event association studies
Authors: Lu Haojie , Wei Yongyue , Jiang Zhou , Zhang Jinhui , Wang Ting , Huang Shuiping , Zeng Ping
Published: October 2021

Background

Integrating functional annotations into SNP-set association studies has been proven a powerful analysis strategy. Statistical methods for such integration have been developed for continuous and binary phenotypes; however, the SNP-set integrative approaches for time-to-event or survival outcomes are lacking.

Methods

We here propose IEHC, an integrative eQTL (expression quantitative trait loci) hierarchical Cox regression, for SNP-set based survival association analysis by modeling effect sizes of genetic variants as a function of eQTL via a hierarchical manner. Three p-values combination tests are developed to examine the joint effects of eQTL and genetic variants after a novel decorrelated modification of statistics for the two components. An omnibus test (IEHC-ACAT) is further adapted to aggregate the strengths of all available tests.

Results

Simulations demonstrated that the IEHC joint tests were more powerful if both eQTL and genetic variants contributed to association signal, while IEHC-ACAT was robust and often outperformed other approaches across various simulation scenarios. When applying IEHC to ten TCGA cancers by incorporating eQTL from relevant tissues of GTEx, we revealed that substantial correlations existed between the two types of effect sizes of genetic variants from TCGA and GTEx, and identified 21 (9 unique) cancer-associated genes which would otherwise be missed by approaches not incorporating eQTL.

Conclusion

IEHC represents a flexible, robust, and powerful approach to integrate functional omics information to enhance the power of identifying association signals for the survival risk of complex human cancers.
Inoculation of mother’s own milk could personalize pasteurized donor human milk used for feeding preterm infants
Authors: Mallardi D. , Tabasso C. , Piemontese P. , Morandi S. , Silvetti T. , Biscarini F. , Cremonesi P. , Castiglioni B. , Pica V. , Stuknyte M. , De Noni I. , Amato O. , Liotto N. , Mosca F. , Roggero P.
Published: October 2021

Background

Human milk is a vehicle for bioactive compounds and beneficial bacteria which promote the establishment of a healthy gut microbiome of newborns, especially of preterm infants. Pasteurized donor human milk (PDHM) is the second-best option when preterm mother’s own milk is unavailable. Since pasteurization affect the microbiological quality of donor milk, PDHM was inoculated with different preterm milk samples and then incubated, in order to evaluate the effect in terms of bacterial growth, human milk microbiome and proteolytic phenomena.

Methods

In an in-vitro study PDHM was inoculated at 10% v/v using ten preterm milk samples. Microbiological, metataxonomic and peptidomic analyses, on preterm milk samples at the baseline (T0), on PDHM and on inoculated milk (IM) samples at T0, after 2 h (T1) and 4 h (T2) of incubation at 37 °C, were conducted.

Results

IM samples at T2 showed a Total Bacterial Count not significantly different (p > 0.01) compared to preterm milk samples. At T2 lactic acid bacteria level was restored in all IM. After inoculation, metataxonomic analysis in IM samples showed that Proteobacteria remained the predominant phylum while Firmicutes moved from 3% at T1 to 9.4% at T2. Peptidomic profile of IM resembled that of PDHM, incubated for the same time, in terms of number and type of peptides.

Conclusion

The study demonstrated that inoculation of PDHM with mother’s own milk could restore bacterial growth and personalize human milk microbiome in PDHM. This effect could be beneficial because of the presence of maternal probiotic bacteria which make PDHM more similar to mother’s own milk.
Altered Env conformational dynamics as a mechanism of resistance to peptide-triazole HIV-1 inactivators
Authors: Zhang Shiyu , Holmes Andrew P. , Dick Alexej , Rashad Adel A. , Enríquez Rodríguez Lucía , Canziani Gabriela A. , Root Michael J. , Chaiken Irwin M.
Published: October 2021

Background

We previously developed drug-like peptide triazoles (PTs) that target HIV-1 Envelope (Env) gp120, potently inhibit viral entry, and irreversibly inactivate virions. Here, we investigated potential mechanisms of viral escape from this promising class of HIV-1 entry inhibitors.

Results

HIV-1 resistance to cyclic (AAR029b) and linear (KR13) PTs was obtained by dose escalation in viral passaging experiments. High-level resistance for both inhibitors developed slowly (relative to escape from gp41-targeted C-peptide inhibitor C37) by acquiring mutations in gp120 both within (Val255) and distant to (Ser143) the putative PT binding site. The similarity in the resistance profiles for AAR029b and KR13 suggests that the shared IXW pharmacophore provided the primary pressure for HIV-1 escape. In single-round infectivity studies employing recombinant virus, V255I/S143N double escape mutants reduced PT antiviral potency by 150- to 3900-fold. Curiously, the combined mutations had a much smaller impact on PT binding affinity for monomeric gp120 (four to ninefold). This binding disruption was entirely due to the V255I mutation, which generated few steric clashes with PT in molecular docking. However, this minor effect on PT affinity belied large, offsetting changes to association enthalpy and entropy. The escape mutations had negligible effect on CD4 binding and utilization during entry, but significantly altered both binding thermodynamics and inhibitory potency of the conformationally-specific, anti-CD4i antibody 17b. Moreover, the escape mutations substantially decreased gp120 shedding induced by either soluble CD4 or AAR029b.

Conclusions

Together, the data suggest that the escape mutations significantly modified the energetic landscape of Env’s prefusogenic state, altering conformational dynamics to hinder PT-induced irreversible inactivation of Env. This work therein reveals a unique mode of virus escape for HIV-1, namely, resistance by altering the intrinsic conformational dynamics of the Env trimer.