bluuebunny/crossref_metadata_2025 huggingface dataset:
“Most of the cases are very similar.”: Documenting and corroborating conflict-related sexual violence affecting Rohingya refugees
Authors: Green Lindsey , McHale Thomas , Mishori Ranit , Kaljee Linda , Akter Chowdhury Shahanoor
Published: April 2022

Background

In August 2017, a large population of Rohingya from northern Rakhine state in Myanmar fled to Bangladesh due to “clearance operations” by the Myanmar security forces characterized by widespread and systematic violence, including extensive conflict-related sexual violence (CRSV). This study sought to document the patterns of injuries and conditions experienced by the Rohingya, with a specific focus on sexual violence.

Methods

Qualitative interviews were conducted with 26 health care professionals who cared for Rohingya refugees after their arrival in Bangladesh between November 2019 and August 2020.

Results

Health care workers universally reported hearing accounts and seeing evidence of sexual and gender-based violence committed against Rohingya people of all genders by the Myanmar military and security forces. They observed physical and psychological consequences of such acts against the Rohingya while patients were seeking care. Health care workers shared that patients faced pressure not to disclose their experiences of CRSV, likely resulted in an underreporting of the prevalence of sexual violence. Forced witnessing of sexual violence and observed increases in pregnancy and birth rates as a result of rape are two less-reported issues that emerged from these data.

Conclusions

Healthcare workers corroborated previous reports that the Rohingya experienced CRSV at the hands of the Myanmar military and security forces. Survivors often revealed their experiences of sexual violence while seeking care for a variety of physical and psychological conditions. Stigma, cultural pressure, and trauma created barriers to disclosing experiences of sexual violence and likely resulted in an underreporting of the prevalence of sexual violence. The findings of this research emphasize the importance of offering universal and comprehensive trauma-informed services to all refugees with the presumption of high rates of trauma in this population and many survivors who may never identify themselves as such.
Transitions between versions of the International Classification of Diseases and chronic disease prevalence estimates from administrative health data: a population-based study
Authors: Sanusi Ridwan A. , Yan Lin , Hamad Amani F. , Ayilara Olawale F. , Vasylkiv Viktoriya , Jozani Mohammad Jafari , Banerji Shantanu , Delaney Joseph , Hu Pingzhao , Wall-Wieler Elizabeth , Lix Lisa M.
Published: April 2022

Background

Diagnosis codes in administrative health data are routinely used to monitor trends in disease prevalence and incidence. The International Classification of Diseases (ICD), which is used to record these diagnoses, have been updated multiple times to reflect advances in health and medical research. Our objective was to examine the impact of transitions between ICD versions on the prevalence of chronic health conditions estimated from administrative health data.

Methods

Study data (i.e., physician billing claims, hospital records) were from the province of Manitoba, Canada, which has a universal healthcare system. ICDA-8 (with adaptations), ICD-9-CM (clinical modification), and ICD-10-CA (Canadian adaptation; hospital records only) codes are captured in the data. Annual study cohorts included all individuals 18 + years of age for 45 years from 1974 to 2018. Negative binomial regression was used to estimate annual age- and sex-adjusted prevalence and model parameters (i.e., slopes and intercepts) for 16 chronic health conditions. Statistical control charts were used to assess the impact of changes in ICD version on model parameter estimates. Hotelling’s T2 statistic was used to combine the parameter estimates and provide an out-of-control signal when its value was above a pre-specified control limit.

Results

The annual cohort sizes ranged from 360,341 to 824,816. Hypertension and skin cancer were among the most and least diagnosed health conditions, respectively; their prevalence per 1,000 population increased from 40.5 to 223.6 and from 0.3 to 2.1, respectively, within the study period. The average annual rate of change in prevalence ranged from -1.6% (95% confidence interval [CI]: -1.8, -1.4) for acute myocardial infarction to 14.6% (95% CI: 13.9, 15.2) for hypertension. The control chart indicated out-of-control observations when transitioning from ICDA-8 to ICD-9-CM for 75% of the investigated chronic health conditions but no out-of-control observations when transitioning from ICD-9-CM to ICD-10-CA.

Conclusions

The prevalence of most of the investigated chronic health conditions changed significantly in the transition from ICDA-8 to ICD-9-CM. These results point to the importance of considering changes in ICD coding as a factor that may influence the interpretation of trend estimates for chronic health conditions derived from administrative health data.
Evaluating the association between socioeconomic position and cardiometabolic risk markers in young adulthood by different life course models
Authors: Kempel Mia Klinkvort , Winding Trine Nøhr , Böttcher Morten , Andersen Johan Hviid
Published: April 2022

Background

Cardiometabolic health in adulthood is associated with socioeconomic position (SEP) in childhood. Although this has been studied by previous research several questions need to be addressed. E.g. knowledge about the association with timing, extent of the exposure as well as lifestyle and adult SEP, is essential to address the increasing social gradient in cardiometabolic diseases.

Methods

This study included a sub-sample (N = 264, 50% women, age 28–30) from an ongoing cohort study. We used a combination of national registers, longitudinal questionnaire data and clinical data. We examined the association between childhood SEP and cardiometabolic risk, measured by a score of multiple risk markers in young adulthood. SEP-indicators included mother’s educational level and household income. The association was evaluated by four different life course models; the latent effects model, the pathway model, the cumulative model and the social mobility model.

Results

We found an inverse association between mother’s educational level and cardiometabolic risk. The association was statistically significant evaluated by the pathway and cumulative life course models, however statistically insignificant evaluated by the latent effects model. No specific association with social mobility was observed. However, high adult educational level seems to have a protecting impact on the association. No association was found between household income and cardiometabolic risk in any of the applied life course models.

Conclusion

Low childhood SEP, represented by mother’s educational level but not household income, is associated with increased cardiometabolic risk in young adulthood. The accumulation of exposure, lifestyle and adult educational attainment are important for the association. In contrast, intergenerational social mobility does not seem to have a specific impact on the association and we find no evidence for a particular timing in childhood.
Splenic infarction after Epstein–Barr virus infection in a patient with hereditary spherocytosis: a case report and literature review
Authors: Ma Zhongwu , Wang Zhejin , Zhang Xiaodan , Yu Haibo
Published: April 2022

Background

Hereditary spherocytosis (HS) complicated by splenic infarction is very rare, and it is even rarer to develop splenic infarction after infectious mononucleosis (IM) as a result of Epstein–Barr virus (EBV) infection. Therefore, misdiagnosis or missed diagnosis is prone to occur.

Case presentation

A 19-year-old Chinese female previously diagnosed with HS was admitted to our institution with persistent high fever and icterus. On admission, the physical examination showed anemia, jaundice, marked splenomegaly, obvious tenderness in the left upper abdomen (LUA). Peripheral blood film shows that spherical red blood cells accounted for about 6%, and Immunoglobulin M (IgM) antibodies specific to Epstein–Barr virus (EBV) viral capsid antigen were detected. An abdominal CT scan revealed a splenic infarction. The patient was diagnosed with HS with splenic infarction following EBV infection and underwent an emergency laparoscopic splenectomy (LS). Pathological analysis showed a splenic infarction with red pulp expansion, white pulp atrophy and a splenic sinus filled with red blood cells. After two months of follow-up visits, the patient showed no signs of relapse.

Conclusions

HS complicated by splenic infarction is very rare and mostly occurs in men under 20 years of age and is often accompanied by other diseases, such as sickle cell traits (SCT) or IM. Although symptomatic management may be sufficient, emergency laparoscopic splenectomy may be safe and effective when conservative treatment is ineffective.
Antibacterial efficacy of peracetic acid in comparison with sodium hypochlorite or chlorhexidine against Enterococcus faecalis and Parvimonas micra
Authors: Briseño-Marroquín Benjamín , Callaway Angelika , Shalamzari Natascha Gol , Wolf Thomas Gerhard
Published: April 2022

Background

The main goal of an endodontic treatment is a complete debridement of the root canal system; however, currently mechanical shaping and chemical cleaning procedures for this purpose have deemed non-satisfactory.

Methods

The efficacy of peracetic acid (PAA; 0.5, 1.0, 2.0%), as a root canal irrigation solution, against Enterococcus faecalis (DSM 20478) and Parvimonas micra (DSM 20468) when compared with the one of sodium hypochlorite (NaOCI; 1.0, 3.0, 5.0%), chlorhexidine digluconate (CHX; 0.12, 0.2, 2.0%) and 0.9% NaCI (as a control solution) was in vitro investigated with the agar diffusion and direct contact methods. The inhibition zone diameters observed with the agar diffusion test were determined. The viable bacterial counts (CFU/ml) were calculated with the direct method.

Results

The agar diffusion test showed that all three root canal irrigation solutions had an efficacy against E. faecalis at all concentrations. The largest inhibition zone diameters against E. faecalis were observed with 5.0% NaOCI. At all three concentrations of PAA, NaOCI, and CHX, the inhibition zone diameter increased with increase in concentration. For P. micra, PAA had a similar inhibition zone diameter despite a concentration increase. In contrast, for NaOCI and CHX, the inhibition zone diameter increased with increasing concentration. 2.0% CHX produced the largest inhibition zone diameter against P. micra. For E. faecalis, only the comparison between 2.0% PAA and 5.0% NaOCI showed statistical significance (p = 0.004). For P. micra the efficacy comparison between the lowest, middle, and highest concentrations of each solution, a statistical significance (p < 0.05) was found for all three solutions. After direct contact with PAA, NaOCI and CHX, no viable bacteria could be determined for either P. micra or E. faecalis.

Conclusions

PAA had a similar antibacterial efficacy as the one of NaOCl and CHX when in direct contact with E. faecalis and P. micra. In the agar diffusion test, PAA showed a similar antibacterial efficacy as the one of CHX and a lower one as the one of NaOCl for E. faecalis.
Identification of microRNA–mRNA–TF regulatory networks in periodontitis by bioinformatics analysis
Authors: Gao Xiaoli , Zhao Dong , Han Jing , Zhang Zheng , Wang Zuomin
Published: April 2022

Background

Periodontitis is a complex infectious disease with various causes and contributing factors. The aim of this study was to identify key genes, microRNAs (miRNAs) and transcription factors (TFs) and construct a miRNA–mRNA–TF regulatory networks to investigate the underlying molecular mechanism in periodontitis.

Methods

The GSE54710 miRNA microarray dataset and the gene expression microarray dataset GSE16134 were downloaded from the Gene Expression Omnibus database. The differentially expressed miRNAs (DEMis) and mRNAs (DEMs) were screened using the “limma” package in R. The intersection of the target genes of candidate DEMis and DEMs were considered significant DEMs in the regulatory network. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Subsequently, DEMs were uploaded to the STRING database, a protein–protein interaction (PPI) network was established, and the cytoHubba and MCODE plugins were used to screen out key hub mRNAs and significant modules. Ultimately, to investigate the regulatory network underlying periodontitis, a global triple network including miRNAs, mRNAs, and TFs was constructed using Cytoscape software.

Results

8 DEMis and 121 DEMs were found between the periodontal and control groups. GO analysis showed that mRNAs were most significantly enriched in positive regulation of the cell cycle, and KEGG pathway analysis showed that mRNAs in the regulatory network were mainly involved in the IL-17 signalling pathway. A PPI network was constructed including 81 nodes and 414 edges. Furthermore, 12 hub genes ranked by the top 10% genes with high degree connectivity and five TFs, including SRF, CNOT4, SIX6, SRRM3, NELFA, and ONECUT3, were identified and might play crucial roles in the molecular pathogenesis of periodontitis. Additionally, a miRNA–mRNA–TF coregulatory network was established.

Conclusion

In this study, we performed an integrated analysis based on public databases to identify specific TFs, miRNAs, and mRNAs that may play a pivotal role in periodontitis. On this basis, a TF–miRNA–mRNA network was established to provide a comprehensive perspective of the regulatory mechanism networks of periodontitis.
Using artificial intelligence reading label system in diabetic retinopathy grading training of junior ophthalmology residents and medical students
Authors: Han Ruoan , Yu Weihong , Chen Huan , Chen Youxin
Published: April 2022

Purpose

Evaluate the efficiency of using an artificial intelligence reading label system in the diabetic retinopathy grading training of junior ophthalmology resident doctors and medical students.

Methods

Loading 520 diabetic retinopathy patients’ colour fundus images into the artificial intelligence reading label system. Thirteen participants, including six junior ophthalmology residents and seven medical students, read the images randomly for eight rounds. They evaluated the grading of images and labeled the typical lesions. The sensitivity, specificity, and kappa scores were determined by comparison with the participants’ results and diagnosis gold standards.

Results

Through eight rounds of reading, the average kappa score was elevated from 0.67 to 0.81. The average kappa score for rounds 1 to 4 was 0.77, and the average kappa score for rounds 5 to 8 was 0.81. The participants were divided into two groups. The participants in Group 1 were junior ophthalmology resident doctors, and the participants in Group 2 were medical students. The average kappa score of Group 1 was elevated from 0.71 to 0.76. The average kappa score of Group 2 was elevated from 0.63 to 0.84.

Conclusion

The artificial intelligence reading label system is a valuable tool for training resident doctors and medical students in performing diabetic retinopathy grading.
Dealing with sexual boundary violation in mental healthcare institutions by government policies: the case of Flanders, Belgium
Authors: Vesentini Lara , Dewilde Kim , Matthys Frieda , De Wachter Dirk , Van Puyenbroeck Hubert , Bilsen Johan
Published: April 2022

Background

To prevent sexual boundary violations (SBV) in mental health care institutions overall governments require these institutions to report SBV incidents to a central registry and to develop institutional guidelines how to react. In Europe SBV policies are only recently developed or implemented, as is also the case in Flanders (Belgium). The implementation of a new institutional policy is always a challenge and can encounter resistance, especially when it concerns SBV, because they remain delicate and complex.

Method

This study evaluated the extent to which mandatory policies on SBV have been implemented in mental health care institutions in Flanders, and possible factors for (non-)implementation of these policies. An online survey was sent to the executives of all mental health care institutions in Flanders (N = 162).

Results

In total 56 executives of mental health care institutions filled out the survey (response rate 35%). Results showed that the implementation of an SBV policy in mental health care institutions is unfortunately inadequate and not all SBV incidents were reported to the central registry. Type of institution and opinions on the SBV policy were related to the (non-)implementation of the requirements.

Conclusions

It is recommended that governments regularly communicate with mental health care institutions to better understand the concerns and difficulties concerning implementation of the required SBV policy and to support/stimulate an organisational culture of more openness and safety on this topic.
Medical documentation practice and associated factors among health workers at private hospitals in the Amhara region, Ethiopia 2021
Authors: Kasaye Mulugeta Desalegn , Beshir Miftah Abdella , Endehabtu Berhanu Fikadie , Tilahun Binyam , Guadie Habtamu Alganeh , Awol Shekur Mohammed , Kalayou Mulugeta Hayelom , Yilma Tesfahun Melese
Published: April 2022

Introduction

Medical documentation is an important part of the medical process as it is an essential way of communication within the health care system. However, medical documentation practice in the private sector is not well studied in Ethiopian context. The aim of this study was to assess the practice of medical documentation and its associated factors among health workers at private hospitals in the Amhara region, Ethiopia.

Method

An institution-based cross-sectional quantitative study supplemented with a qualitative design was conducted among 419 health workers at the private hospitals in the Amhara Region, Ethiopia from March 29 to April 29 /2021. Data were collected using both a self-administered questionnaire and interview guide for quantitative and qualitative respectively. Data were entered using Epi data version 3.1 and analyzed using SPSS version 20. Descriptive statistics, Bi-variable, and multivariable logistic regression analysis were performed. In-depth interviews were conducted using semi-structured questionnaires with eight respondents to explore the challenges related to the practice of medical documentation. Respondent’s response were analyzed using OpenCode version 4.03 thematically.

Results

Four hundred seven study participants returned the questionnaire. Nearly 50 % (47.2%) health workers had of good medical documentation practice. Health workers who received in-service training on medical documentation AOR = 2.77(95% CI: [1.49,5.14]), good knowledge AOR = 2.28 (95% CI: [1.34,3.89]), favorable attitude AOR = 1.78 (95%CI: [1.06,2.97]), strong motivation AOR = 3.49 (95% CI: [2.10,5.80]), available guide line formats AOR = 3.12 (95% CI: [1.41,6.84]), eHealth literacy AOR = 1.73(95% CI: [1.02,2.96]), younger age AOR = 2.64 (95% CI:[1.27,5.46]) were statistically associated with medical documentation.

Conclusion

More than half of the medical services provided were not registered. Therefore, it is important to put extra efforts to improve documentation practice by providing planed trainings on standards of documentation to all health workers, creating positive attitudes and enhancing their knowledge by motivating them to develop a culture of information.
Assessing the pharmaceutical care provision to suspected COVID-19 patients in community pharmacies: a simulated patient study
Authors: Karout Samar , Khojah Hani M. J. , Itani Rania , Jaffal Fatima , El-Lakany Abdalla
Published: April 2022

Background

In the wake of COVID-19, community pharmacists (CP) were called upon to free up healthcare providers to treat more serious conditions and alleviate overcrowded healthcare centers. CPs were placed under tremendous pressure, where many patients primarily sought their health advice. This situation raised concerns about the preparedness of CPs in facing these challenges. Therefore, this study aimed to assess the appropriateness of pharmaceutical care provided by CPs to patients with suspected COVID-19 and to investigate their communication skills.

Methods

A simulated patient (SP) study was conducted among randomly selected community pharmacies in Beirut, Lebanon. Each pharmacy was visited by the SP who complained of fever and loss of smell sensation. Interactions between the attending pharmacist and the suspected COVID-19 patient were documented directly after each visit in a standardized data collection form.

Results

More than half of the CPs (56%) did not retrieve any relevant information to assess the patient’s condition. While pharmacists’ responses were limited to one to two recommendations, with the majority recommending the patient to perform the PCR test (90%). Inappropriate recommendations made by the CPs included mainly the confirmation that the patient had COVID-19 without prior testing (9%), and prescribing either an antimicrobial drug (5%) or dietary supplements (20%), claiming that the latter are essential to boost the patient’s immunity. As for the pharmacist-patient communication skills, the mean total score was 2.25 ± 0.79 (out of 4), displaying nonoptimal and ineffective communication.

Conclusion

An unsatisfactory and suboptimal provision of pharmaceutical care to a suspected COVID-19 case was evident. This may be a public health threat, particularly for developing countries that lack an efficient and unified healthcare system. The findings should alert health authorities to support and guide community pharmacists in assisting suspected COVID-19 patients.
Effectiveness of checklist-based box system intervention (CBBSI) versus routine care on improving utilization of antenatal care visits in Northwest Ethiopia: a cluster randomized controlled trial
Authors: Andargie Netsanet Belete , Debelew Gurmesa Tura
Published: April 2022

Background

In Ethiopia, the proportion of mothers who attend the fourth antenatal care visit is lower than the proportion who attend the first visit. Although the reasons for these dropouts were investigated, few studies introduced interventions to promote the fourth antenatal care visit. Hence, the aim of this study was to assess the effectiveness of checklist-based box system intervention on improving fourth antenatal care visit.

Method

This study employed a double-blind, parallel-group, two-arm cluster randomized controlled trial to compare the effectiveness of checklist-based box system intervention with the usual standard of care as a control arm. Study clusters are assigned to intervention and control arm in 1:1 allocation ratio using simple randomization technique. Pregnant mothers below 16 weeks of gestation were enrolled. Open data kit was used to collect data from the baseline and end-line surveys, and STATA version 15.0 was used to analyse the data. A difference-in-difference estimator was used to compare fourth antenatal care visit between the intervention and control groups across time. Mixed effect multi-level logistic regression was used to examine the relationship between the dependent and independent variables.

Result

Data were collected from 2224 mothers who belong to 15 intervention and 15 control clusters. The difference in difference estimation resulted in a significant difference (26.1, 95%CI: 18–34%, p < 0.0001) between the intervention and control groups. Similarly, as compared to controls, the fourth antenatal care visit was found significantly higher in the intervention clusters (432 (85.2%) Vs. 297 (53.7%), p < 0.0001)/(AOR:5.69, 95% CI:4.14–7.82). Mothers who were knowledgeable about the services given during antenatal care visits (AOR: 2.31, 95% CI:1.65–3.24) and mothers who had a high level of social support (AOR:1.47, 95% CI: 1.06–2.04) were more likely to attend the fourth antenatal care visit.

Conclusion

Implementation of checklist-based box system intervention resulted in a statistically significant effect in attendance of fourth antenatal care visit. Community-level variables were found to be more important in explaining variability in the fourth antenatal care visit. It is recommended that the intervention be implemented on a larger scale.

Trial registration

ClinicalTrials.gov, Retrospectively registered on 26/03/2019, with trial registration number-NCT03891030.
Hospital treatment costs associated with incident complications in patients with type 2 diabetes—real-world study based on electronic patient information systems
Authors: Sund Reijo , Peltonen Tuomas , Lehtimäki Aku-Ville , Martikainen Janne
Published: April 2022

Background

Type 2 diabetes (T2D) and its complications cause a significant public health and economic challenge. To enable the optimal resource allocation across different prevention and treatment policies for the management of T2D-related complications, detailed cost estimates related to the complications of T2D are needed. Therefore, the objective of the study was to provide reliable and sufficiently detailed real-world estimates of costs associated with different T2D complications in a Finnish university hospital setting.

Methods

A cohort of T2D patients living in the catchment area of a university hospital during 2012 and 2016 was identified from the comprehensive national FinDM diabetes database for longitudinal assessment of T2D associated complication treatment costs. Data on patient-level events were extracted from the FinDM data and complemented with all accountable services and related detailed costing data gathered from the university hospital’s electronic patient information systems by using unique personal identity codes. Patients were screened for their first diagnoses of complications using the same national quality registry definitions as in the FinDM database. Multivariable gamma regression model with a log link function was applied to study the association between baseline factors and complication costs. In addition, an interactive online tool was developed to create predicted costs for complication costs with selected baseline factors.

Results

A total of 27 255 prevalent and incident patients with T2D were identified from the national FinDM register. Finally, a total of 16 148 complication episodes for 7 895 patients were included in the cost analyses. The mean estimated one-year hospital treatment costs of T2D-related complication varied from 6 184 to 24 507 euros per complication. Regression analyses showed that coexisting conditions are significantly associated with initial and recurrent complication costs.

Conclusions

The study shows updated Finnish cost estimates and their main cost drivers for T2D-related complications treated in the university hospital setting. The results of our study highlight the significance of guideline implementation, effective preventive treatments for T2D, as well as the importance of treatment adherence to avoid these costly complications.
Prevalence of porcine parvovirus 1 through 7 (PPV1-PPV7) and co-factor association with PCV2 and PRRSV in Korea
Authors: Kim Seung-Chai , Kim Jae-Hong , Kim Jae-Yeob , Park Gyeong-Seo , Jeong Chang-Gi , Kim Won-Il
Published: April 2022

Background

Classical porcine parvovirus (PPV1) and novel porcine parvoviruses designated porcine parvovirus 2 through 7 (PPV2-PPV7) are widespread in pig populations. The objective of this study was to investigate the prevalence rates of PPV1-PPV7 in Korea by detecting PPVs in serum, lung and fecal samples and to elucidate the association of PPVs with porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory virus (PRRSV), major pathogens involved in porcine respiratory disease complex (PRDC). A total of 286 serum, 481 lung, and 281 fecal samples collected from 2018 to 2020 were analyzed.

Results

The results showed that PPVs are widespread in Korea; the highest detection rates were found in lung samples and ranged from 7.9% (PPV1) to 32.6% (PPV2). Regarding age groups, fattening pigs had the highest detection rates of PPVs, ranging from 6.4% (PPV1) to 36.5% (PPV6); this finding suggests the chronic nature of PPV infections and the continual circulation of these viruses. When compared with PCV2- and PRRSV-negative lung samples, PCV2-positive samples with or without PRRSV positivity had significantly higher detection levels of PPV1 and PPV6. In contrast, the prevalence of PPV2 and PPV7 was significantly higher in PRRSV-infected lung samples regardless of PCV2 detection. PPV5 was detected significantly more frequently in samples  with both PCV2 and PRRSV positivity.

Conclusions

This study could offer a better understanding of the role of PPVs in PCV2 and/or PRRSV infection though further studies are needed to experimentally assess the impact of PPVs in coinfections.
Liraglutide preserves CD34+ stem cells from dysfunction Induced by high glucose exposure
Authors: Sforza Annalisa , Vigorelli Vera , Rurali Erica , Perrucci Gianluca Lorenzo , Gambini Elisa , Arici Martina , Metallo Alessia , Rinaldi Raffaella , Fiorina Paolo , Barbuti Andrea , Raucci Angela , Sacco Elena , Rocchetti Marcella , Pompilio Giulio , Genovese Stefano , Vinci Maria Cristina
Published: April 2022

Background

Glucagon like peptide-1 receptor agonists (GLP-1RAs) have shown to reduce mortality and cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Since the impairment in number and function of vasculotrophic circulating CD34+ hematopoietic stem progenitor cells (HSPCs) in T2D has been reported to increase cardiovascular (CV) risk, we hypothesized that one of the mechanisms whereby GLP-1 RAs exert CV protective effects may be related to the ability to improve CD34+ HSPC function.

Methods

In cord blood (CB)-derived CD34+ HSPC, the expression of GLP-1 receptor (GLP-1R) mRNA, receptor protein and intracellular signaling was evaluated by RT-qPCR and Western Blot respectively. CD34+ HSPCs were exposed to high glucose (HG) condition and GLP-1RA liraglutide (LIRA) was added before as well as after functional impairment. Proliferation, CXCR4/SDF-1α axis activity and intracellular ROS production of CD34+ HSPC were evaluated.

Results

CD34+ HSPCs express GLP-1R at transcriptional and protein level. LIRA treatment prevented and rescued HSPC proliferation, CXCR4/SDF-1α axis activity and metabolic imbalance from HG-induced impairment. LIRA stimulation promoted intracellular cAMP accumulation as well as ERK1/2 and AKT signaling activation. The selective GLP-1R antagonist exendin (9–39) abrogated LIRA-dependent ERK1/2 and AKT phosphorylation along with the related protective effects.

Conclusion

We provided the first evidence that CD34+ HSPC express GLP-1R and that LIRA can favorably impact on cell dysfunction due to HG exposure. These findings open new perspectives on the favorable CV effects of GLP-1 RAs in T2DM patients.
Towards an understanding of oleate hydratases and their application in industrial processes
Authors: Prem Sophia , Helmer Carl P. O. , Dimos Nicole , Himpich Stephanie , Brück Thomas , Garbe Daniel , Loll Bernhard
Published: April 2022

Fatty acid hydratases are unique to microorganisms. Their native function is the oxidation of unsaturated C–C bonds to enable detoxification of environmental toxins. Within this enzyme family, the oleate hydratases (Ohys), which catalyze the hydroxylation of oleic acid to 10-(R)-hydroxy stearic acid (10-HSA) have recently gained particular industrial interest. 10-HSA is considered to be a replacement for 12-(R)-hydroxy stearic acid (12-HSA), which has a broad application in the chemical and pharmaceutical industry. As 12-HSA is obtained through an energy consuming synthesis process, the biotechnological route for sustainable 10-HSA production is of significant industrial interest. All Ohys identified to date have a non-redox active FAD bound in their active site. Ohys can be divided in several subfamilies, that differ in their oligomerization state and the decoration with amino acids in their active sites. The latter observation indicates a different reaction mechanism across those subfamilies. Despite intensive biotechnological, biochemical and structural investigations, surprising little is known about substrate binding and the reaction mechanism of this enzyme family. This review, summarizes our current understanding of Ohys with a focus on sustainable biotransformation.
One-pot biosynthesis of 7β-hydroxyandrost-4-ene-3,17-dione from phytosterols by cofactor regeneration system in engineered mycolicibacterium neoaurum
Authors: Zhao Yun-Qiu , Liu Yong-Jun , Ji Wei-Ting , Liu Kun , Gao Bei , Tao Xin-Yi , Zhao Ming , Wang Feng-Qing , Wei Dong-Zhi
Published: April 2022

Background

7β-hydroxylated steroids (7β-OHSt) possess significant activities in anti-inflammatory and neuroprotection, and some of them have been widely used in clinics. However, the production of 7β-OHSt is still a challenge due to the lack of cheap 7β-hydroxy precursor and the difficulty in regio- and stereo-selectively hydroxylation at the inert C7 site of steroids in industry. The conversion of phytosterols by Mycolicibacterium species to the commercial precursor, androst-4-ene-3,17-dione (AD), is one of the basic ways to produce different steroids. This study presents a way to produce a basic 7β-hydroxy precursor, 7β-hydroxyandrost-4-ene-3,17-dione (7β-OH-AD) in Mycolicibacterium, for 7β-OHSt synthesis.

Results

A mutant of P450-BM3, mP450-BM3, was mutated and engineered into an AD producing strain for the efficient production of 7β-OH-AD. The enzyme activity of mP450-BM3 was then increased by 1.38 times through protein engineering and the yield of 7β-OH-AD was increased from 34.24 mg L− 1 to 66.25 mg L− 1. To further enhance the performance of 7β-OH-AD producing strain, the regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) for the activity of mP450-BM3-0 was optimized by introducing an NAD kinase (NADK) and a glucose-6-phosphate dehydrogenase (G6PDH). Finally, the engineered strain could produce 164.52 mg L− 1 7β-OH-AD in the cofactor recycling and regeneration system.

Conclusions

This was the first report on the one-pot biosynthesis of 7β-OH-AD from the conversion of cheap phytosterols by an engineered microorganism, and the yield was significantly increased through the mutation of mP450-BM3 combined with overexpression of NADK and G6PDH. The present strategy may be developed as a basic industrial pathway for the commercial production of high value products from cheap raw materials.
Comparison of household socioeconomic status classification methods and effects on risk estimation: lessons from a natural experimental study, Kisumu, Western Kenya
Authors: Were Vincent , Foley Louise , Turner-Moss Eleanor , Mogo Ebele , Wadende Pamela , Musuva Rosemary , Obonyo Charles
Published: April 2022

Introduction

Low household socioeconomic status is associated with unhealthy behaviours including poor diet and adverse health outcomes. Different methods leading to variations in SES classification has the potential to generate spurious research findings or misinform policy. In low and middle-income countries, there are additional complexities in defining household SES, a need for fieldwork to be conducted efficiently, and a dearth of information on how classification could impact estimation of disease risk.

Methods

Using cross-sectional data from 200 households in Kisumu County, Western Kenya, we compared three approaches of classifying households into low, middle, or high SES: fieldworkers (FWs), Community Health Volunteers (CHVs), and a Multiple Correspondence Analysis econometric model (MCA). We estimated the sensitivity, specificity, inter-rater reliability and misclassification of the three methods using MCA as a comparator. We applied an unadjusted generalized linear model to determine prevalence ratios to assess the association of household SES status with a self-reported diagnosis of diabetes or hypertension for one household member.

Results

Compared with MCA, FWs successfully classified 21.7% (95%CI = 14.4%-31.4%) of low SES households, 32.8% (95%CI = 23.2–44.3) of middle SES households, and no high SES households. CHVs successfully classified 22.5% (95%CI = 14.5%-33.1%) of low SES households, 32.8% (95%CI = 23.2%-44.3%) of middle SES households, and no high SES households. The level of agreement in SES classification was similar between FWs and CHVs but poor compared to MCA, particularly for high SES. None of the three methods differed in estimating the risk of hypertension or diabetes.

Conclusions

FW and CHV assessments are community-driven methods for SES classification. Compared to MCA, these approaches appeared biased towards low or middle SES households and not sensitive to high household SES. The three methods did not differ in risk estimation for diabetes and hypertension. A mix of approaches and further evaluation to refine SES classification methodology is recommended.
The number of cycles of adjuvant chemotherapy in stage III and high-risk stage II rectal cancer: a nomogram and recursive partitioning analysis
Authors: Chen Wei-Wei , Wang Wen-Ling , Dong Hong-Min , Wang Gang , Li Xiao-Kai , Li Guo-Dong , Chen Wang-Hua , Chen Juan , Bai Sai-Xi
Published: April 2022

Objective

The prognostic role of the number of cycles of adjuvant chemotherapy (ACT) after total mesorectal excision in stage III and high-risk stage II rectal cancer is unknown. As a result of this, our study was designed to assess the effect of the number of cycles of ACT on the prediction of cancer-specific survival.

Methods

Four hundred patients that were diagnosed as stage III and high-risk stage II rectal cancer from January 2012 to January 2018 and who had received total mesorectal excision were enrolled in this study. A nomogram incorporating the number of cycles of ACT was also developed in this study. For internal validation, the bootstrap method was used and the consistency index was used to evaluate the accuracy of the model. The patients were stratified into risk groups according to their tumor characteristics by recursive partitioning analysis.

Results

We found that the risk of death was decreased by 26% (HR = 0.74, 95% CI: 0.61–0.89, P = 0.0016) with each increasing ACT cycle. The N stage, positive lymph node ratio (PLNR), carcinoembryonic antigen, neutrophil-to-lymphocyte ratio, and the number of cycles of ACT were chosen and entered into the nomogram model. Recursive partitioning analysis-based risk stratification revealed a significant difference in the prognosis in rectal cancer patients with high-risk, intermediate-risk, and low-risk (3-year cancer-specific survival: 0.246 vs. 0.795 vs. 0.968, P < 0.0001). Seven or more cycles of ACT yielded better survival in patients with PLNR ≥ 0.28 but not in patients with PLNR < 0.28.

Conclusion

In conclusion, the nomogram prognosis model based on the number of cycles of ACT predicted individual prognosis in rectal cancer patients who had undergone total mesorectal excision. These findings further showed that in patients with PLNR ≥ 0.28, no fewer than 7 cycles of ACT are needed to significantly reduce the patient’s risk of death.
β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells?
Authors: Diane Abdoulaye , Al-Shukri Noora Ali , Bin Abdul Mu-u-min Razik , Al-Siddiqi Heba H.
Published: April 2022

Diabetes mellitus (DM), currently affecting 463 million people worldwide is a chronic disease characterized by impaired glucose metabolism resulting from the loss or dysfunction of pancreatic β-cells with the former preponderating in type 1 diabetes (T1DM) and the latter in type 2 diabetes (T2DM). Because impaired insulin secretion due to dysfunction or loss of pancreatic β-cells underlies different types of diabetes, research has focused its effort towards the generation of pancreatic β-cells from human pluripotent stem cell (hPSC) as a potential source of cells to compensate for insulin deficiency. However, many protocols developed to differentiate hPSCs into insulin-expressing β-cells in vitro have generated hPSC-derived β-cells with either immature phenotype such as impaired glucose-stimulated insulin secretion (GSIS) or a weaker response to GSIS than cadaveric islets. In pancreatic β-cells, mitochondria play a central role in coupling glucose metabolism to insulin exocytosis, thereby ensuring refined control of GSIS. Defects in β-cell mitochondrial metabolism and function impair this metabolic coupling. In the present review, we highlight the role of mitochondria in metabolism secretion coupling in the β-cells and summarize the evidence accumulated for the implication of mitochondria in β-cell dysfunction in DM and consequently, how targeting mitochondria function might be a new and interesting strategy to further perfect the differentiation protocol for generation of mature and functional hPSC-derived β-cells with GSIS profile similar to human cadaveric islets for drug screening or potentially for cell therapy.
Phosphorylated ATF1 at Thr184 promotes metastasis and regulates MMP2 expression in gastric cancer
Authors: Li Tong , Cao Huiyuan , Wu Sa , Zhong Peimin , Ding Jie , Wang Jing , Wang Fangfang , He Zhiwei , Huang Guo-Liang
Published: April 2022

Background

Studies have revealed an important role of activating transcription factor 1 (ATF1) and phosphorylated ATF1 at Ser63 in tumors. Our previous study identified Thr184 as a novel phosphorylation site of ATF1. However, the role of phosphorylated ATF1 at Thr184 (p-ATF1-T184) in tumor is unclear. This study figured out the role of p-ATF1-T184 in the metastasis of gastric cancer (GC) and in the regulation of Matrix metallopeptidase 2 (MMP2).

Methods

Immunohistochemical analysis (IHC) was performed to analyze the level of p-ATF1-T184 and its relationship with clinicopathological characteristics. Wound scratch test, Transwell assay were used to observe the role of p-ATF1-T184 in the invasion and metastasis of GC. The regulation of MMP2 by p-ATF1-T184 was investigated by a series of experiments including quantitative RT-PCR, western blot, gelatin zymography assay, Chromatin immunoprecipitation (ChIP), luciferase reporter assay and cycloheximide experiment. The Cancer Genome Atlas (TCGA) data were used to analyze the expression and prognostic role of ATF1 and MMP2 in GC. Mass spectrometry (MS) following co-immunoprecipitation (co-IP) assay was performed to identify potential upstream kinases that would phosphorylate ATF1 at Thr184.

Results

High expression level of p-ATF1-T184 was found and significantly associated with lymph node metastasis and poor survival in a GC cohort of 126 patients. P-ATF1-T184 promoted migration and invasion of gastric cancer cells. Phosphorylation of ATF1-T184 could regulate the mRNA, protein expression and extracellular activity of MMP2. P-ATF1-T184 further increased the DNA binding ability, transcription activity, and stabilized the protein expression of ATF1. Moreover, TCGA data and IHC results suggested that the mRNA level of ATF1 and MMP2, and protein level of p-ATF1-T184 and MMP2 could be prognosis markers of GC. Two protein kinase related genes, LRBA and S100A8, were identified to be correlated with the expression ATF1 in GC.

Conclusion

Our results indicated that p-ATF1-T184 promoted metastasis of GC by regulating MMP2.
The role of neutrophil elastase in aortic valve calcification
Authors: Liu Yan , Jiang Peng , An Liqin , Zhu Mengying , Li Jin , Wang Yue , Huang Qin , Xiang Yi , Li Xiaorong , Shi Qiong , Weng Yaguang
Published: April 2022

Background

Calcific aortic valve disease (CAVD) is the most commonly valvular disease in the western countries initiated by inflammation and abnormal calcium deposition. Currently, there is no clinical drug for CAVD. Neutrophil elastase (NE) plays a causal role in inflammation and participates actively in cardiovascular diseases. However, the effect of NE on valve calcification remains unclear. So we next explore whether it is involved in valve calcification and the molecular mechanisms involved.

Methods

NE expression and activity in calcific aortic valve stenosis (CAVD) patients (n = 58) and healthy patients (n = 30) were measured by enzyme-linked immunosorbent assay (ELISA), western blot and immunohistochemistry (IHC). Porcine aortic valve interstitial cells (pVICs) were isolated and used in vitro expriments. The effects of NE on pVICs inflammation, apoptosis and calcification were detected by TUNEL assay, MTT assay, reverse transcription polymerase chain reaction (RT-PCR) and western blot. The effects of NE knockdown and NE activity inhibitor Alvelestat on pVICs inflammation, apoptosis and calcification under osteogenic medium induction were also detected by RT-PCR, western blot, alkaline phosphatase staining and alizarin red staining. Changes of Intracellular signaling pathways after NE treatment were measured by western blot. Apolipoprotein E−/− (APOE−/−) mice were employed in this study to establish the important role of Alvelestat in valve calcification. HE was used to detected the thickness of valve. IHC was used to detected the NE and α-SMA expression in APOE−/− mice. Echocardiography was employed to assess the heat function of APOE−/− mice.

Results

The level and activity of NE were evaluated in patients with CAVD and calcified valve tissues. NE promoted inflammation, apoptosis and phenotype transition in pVICs in the presence or absence of osteogenic medium. Under osteogenic medium induction, NE silencing or NE inhibitor Alvelestat both suppressed the osteogenic differentiation of pVICs. Mechanically, NE played its role in promoting osteogenic differentiation of pVICs by activating the NF-κB and AKT signaling pathway. Alvelestat alleviated valve thickening and decreased the expression of NE and α-SMA in western diet-induced APOE−/− mice. Alvelestat also reduced NE activity and partially improved the heart function of APOE−/−mice.

Conclusions

Collectively, NE is highly involved in the pathogenesis of valve calcification. Targeting NE such as Alvelestat may be a potential treatment for CAVD.
Retraction Note: Exosomal DLX6-AS1 from hepatocellular carcinoma cells induces M2 macrophage polarization to promote migration and invasion in hepatocellular carcinoma through microRNA-15a-5p/CXCL17 axis
Authors: Wang Lin-pei , Lin Jing , Ma Xiao-qiu , Xu Dong-yao , Shi Chun-feng , Wang Wei , Jiang Xiao-jie
Published: April 2022

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-021-01973-z.
Past and current status of adolescents living with HIV in South Africa, 2005–2017
Authors: Naidoo Inbarani , Takatshana Sinovuyo , Sewpaul Ronel , Jooste Sean , Siyanai Zhou , Maseko Goitseone , Moyo Sizulu , Zuma Khangelani , Mabaso Musawenkosi , Nompumelelo Zungu
Published: April 2022

Objectives

This paper reports HIV prevalence, incidence, progress towards the UNAIDS (90-90-90) targets, and HIV drug resistance among adolescents living with HIV in South Africa. We conducted secondary analyses using data extracted from the South African national HIV prevalence surveys (2005–2017). Analyses were stratified by sex and age (10–14 and 15–19-years), presenting weighted descriptive statistics, and realised totals.

Results

HIV prevalence increased from 3.0% in 2012 to 3.7% in 2017, translating to 360 582 (95% CI 302 021-419 144) HIV positive adolescents in 2017. Female adolescents bear a disproportionate HIV burden of 5.6% prevalence versus 0.7% for males. HIV incidence remained relatively stable. For the UNAIDS 90-90-90 targets, approximately 62.3% of adolescents knew their HIV status, 65.4% of whom were on antiretroviral therapy, and of these 78.1% on antiretroviral therapy had attained viral load suppression. There are knowledge gaps pertaining to the magnitude of perinatal infections and postnatal infections, and socio-behavioural risk factors for HIV transmission among adolescents in South Africa. There is still a need for focussed interventions targeting adolescent (1) gender disparities in HIV risk (2) screening for HIV, (3) sustained access and adherence to antiretroviral therapy and (3) retention in care to maintain viral load suppression.