bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution and genomic organization of the insect sHSP gene cluster and coordinate regulation in phenotypic plasticity
Authors: Leask Megan , Lovegrove Mackenzie , Walker Abigail , Duncan Elizabeth , Dearden Peter
Published: August 2021

Background

Conserved syntenic gene complexes are rare in Arthropods and likely only retained due to functional constraint. Numerous sHSPs have been identified in the genomes of insects, some of which are located clustered in close proximity. Previous phylogenetic analyses of these clustered sHSP have been limited to a small number of holometabolous insect species and have not determined the pattern of evolution of the clustered sHSP genes (sHSP-C) in insect or Arthropod lineages.

Results

Using eight genomes from representative insect orders and three non-insect arthropod genomes we have identified that a syntenic cluster of sHSPs (sHSP-C) is a hallmark of most Arthropod genomes. Using 11 genomes from Hymenopteran species our phylogenetic analyses have refined the evolution of the sHSP-C in Hymenoptera and found that the sHSP-C is order-specific with evidence of birth-and-death evolution in the hymenopteran lineage. Finally we have shown that the honeybee sHSP-C is co-ordinately expressed and is marked by genomic features, including H3K27me3 histone marks consistent with coordinate regulation, during honeybee ovary activation.

Conclusions

The syntenic sHSP-C is present in most insect genomes, and its conserved coordinate expression and regulation implies that it is an integral genomic component of environmental response in arthropods.
Tomato transcriptomic response to Tuta absoluta infestation
Authors: D’Esposito Daniela , Manzo Daniele , Ricciardi Alessandro , Garonna Antonio Pietro , De Natale Antonino , Frusciante Luigi , Pennacchio Francesco , Ercolano Maria Raffaella
Published: August 2021

Background

The South America pinworm, Tuta absoluta, is a destructive pest of tomato that causes important losses worldwide. Breeding of resistant/tolerant tomato cultivars could be an effective strategy for T. absoluta management but, despite the economic importance of tomato, very limited information is available about its response to this treat. To elucidate the defense mechanisms to herbivore feeding a comparative analysis was performed between a tolerant and susceptible cultivated tomato at both morphological and transcriptome level to highlight constitutive leaf barriers, molecular and biochemical mechanisms to counter the effect of T. absoluta attack.

Results

The tolerant genotype showed an enhanced constitutive barrier possibly as result of the higher density of trichomes and increased inducible reactions upon mild infestation thanks to the activation/repression of key transcription factors regulating genes involved in cuticle formation and cell wall strength as well as of antinutritive enzymes, and genes involved in the production of chemical toxins and bioactive secondary metabolites.

Conclusions

Overall, our findings suggest that tomato resilience to the South America pinworm is achieved by a combined strategy between constitutive and induced defense system. A well-orchestrated modulation of plant transcription regulation could ensure a trade-off between defense needs and fitness costs. Our finding can be further exploited for developing T. absoluta tolerant cultivars, acting as important component of integrated pest management strategy for more sustainable production.
Relation between body composition and severe diarrhea in patients treated with preoperative chemoradiation with capecitabine for rectal cancer: a single-centre cohort study
Authors: van Rees J. M. , Hartman W. , Nuyttens J. J. M. E. , Oomen-de Hoop E. , van Vugt J. L. A. , Rothbarth J. , Verhoef C. , van Meerten E.
Published: August 2021

Background

Chemoradiation with capecitabine followed by surgery is standard care for locally advanced rectal cancer (LARC). Severe diarrhea is considered a dose-limiting toxicity of adding capecitabine to radiation therapy. The aim of this study was to describe the risk factors and the impact of body composition on severe diarrhea in patients with LARC during preoperative chemoradiation with capecitabine.

Methods

A single centre retrospective cohort study was conducted in a tertiary referral centre. All patients treated with preoperative chemoradiation with capecitabine for LARC from 2009 to 2015 were included. Patients with locally recurrent rectal cancer who received chemoradiation for the first time were included as well. Logistic regression analyses were performed to identify risk factors for severe diarrhea.

Results

A total of 746 patients were included. Median age was 64 years (interquartile range 57–71) and 477 patients (64%) were male. All patients received a radiation dosage of 25 × 2 Gy during a period of five weeks with either concomitant capecitabine administered on radiation days or continuously during radiotherapy. In this cohort 70 patients (9%) developed severe diarrhea. In multivariable logistic regression analyses female sex (OR: 4.42, 95% CI 2.54–7.91) and age ≥ 65 (OR: 3.25, 95% CI 1.85–5.87) were the only risk factors for severe diarrhea.

Conclusions

Female patients and patients aged sixty-five or older had an increased risk of developing severe diarrhea during preoperative chemoradiation therapy with capecitabine. No relation was found between body composition and severe diarrhea.
Invasive pneumococcal disease in persons with predisposing factors is dominated by non-vaccine serotypes in Southwest Sweden
Authors: Bergman Karin , Härnqvist Tor , Backhaus Erik , Trollfors Birger , Dahl Mats S. , Kolberg Helena , Ockborn Gunilla , Andersson Rune , Karlsson Johanna , Mellgren Åsa , Skovbjerg Susann
Published: August 2021

Background

The pneumococcal conjugate vaccine PCV7 was introduced in Southwest Sweden in the child vaccination program in 2009, followed by PCV13 in 2010 and PCV10 in 2015. In this retrospective cohort study we assessed the pneumococcal serotype distribution in relation to predisposing factors, clinical manifestations and outcome during seven years after PCV introduction.

Methods

Clinical data from 1278 patients with 1304 episodes of invasive pneumococcal disease (IPD) between January 2009 and December 2015 in Region Västra Götaland, Sweden, were retrospectively collected from medical records. Pneumococcal isolates were serotyped by gel diffusion and/or Quellung reactions performed at the Public Health Agency in Sweden. Associations between serotypes and clinical characteristics were statistically evaluated by use of Fisher’s exact test, Mann-Whitney U test and Logistic regression analysis, whereas IPD episodes caused by serotypes over time were analyzed by Mantel-Haenszel chi-square test.

Results

With the exception of serotype 3, the prevalence of PCV13 serotypes decreased during the study period, from 76% (n = 157) of all IPD episodes in 2009 to 25% (n = 42) in 2015 (p < 0.001) while non-PCV13 serotypes increased, mainly among patients ≥65 years and in patients with predisposing factors, including cardiovascular disease, pulmonary disease and malignancy (p < 0.001 for all). Patients with predisposing factors, including those with malignancy, immune deficiency or renal disease, were more likely to have IPD caused by a serotype not included in PCV13 rather than a vaccine-included serotype. Serotype 3 was associated with intensive care unit admissions while serotype 1 and 7F caused IPD among healthier and younger patients. PCV13 serotypes were associated with invasive pneumonia, and non-PCV13 serotypes were associated with bacteremia with unknown focus and with manifestations other than pneumonia or meningitis.

Conclusions

Non-PCV13 serotypes caused the majority of IPD cases in Southwest Sweden, especially in patients ≥65 years and in patients with predisposing factors. Serotype 3, included in PCV13, was prevalent and often caused severe disease.
Virulence factors and antimicrobial resistance of uropathogenic Escherichia coli (UPEC) isolated from urinary tract infections: a systematic review and meta-analysis
Authors: Bunduki Gabriel Kambale , Heinz Eva , Phiri Vincent Samuel , Noah Patrick , Feasey Nicholas , Musaya Janelisa
Published: August 2021

Background

Uropathogenic Escherichia coli (UPEC) are amongst the most frequent causes of urinary tract infections. We report a systematic review and meta-analysis of virulence factors and antimicrobial resistance of UPEC isolated from urinary tract infections.

Methods

A systematic review and meta-analysis were performed using PRISMA guidelines (Research Registry ref. 5874). Data were extracted from PubMed/MEDLINE and ScienceDirect databases for studies published from January 1, 2000 to December 31, 2019. Studies reporting antimicrobial resistance and virulence factors of UPEC isolated in confirmed urinary tract infections (≥105CFU/ml) were eligible. Prevalence of antimicrobial resistance and virulence factors of UPEC were estimated using random-effects meta-analysis model. Estimates with 95% confidence intervals, I-square (I2) statistic, and Cochran’s Q test were computed using the score statistic and the exact binomial method by incorporating the Freeman-Tukey double arcsine transformation of proportions.

Results

Our search returned 2504 hits, of which 13 studies were included in the meta-analysis, totalling 1888 UPEC isolates. Highest antimicrobial resistance rates were observed among the antibiotic class of tetracycline in 69.1% (498/721), followed by sulphonamides in 59.3% (1119/1888), quinolones in 49.4% (1956/3956), and beta-lactams in 36.9% (4410/11964). Among beta-lactams, high resistance was observed in aminopenicillins in 74.3% (1157/1557) and first generation cephalosporins in 38.8% (370/953). Meanwhile, virulence factors with highest prevalence were immune suppressors (54.1%) followed by adhesins (45.9%). Taken individually, the most observed virulence genes were shiA (92.1%), CSH (80.0%), fimH/MSHA (75.3%), traT (75.1%), sisA (72.2%), iucD (65.7%), iutA (61.8%), kpsMTII (60.6%), and PAI (55.2%).

Conclusions

The increased antibiotic resistance of UPEC isolates was demonstrated and suggested a need for reassessment of empirical therapies in urinary tract infections treatment caused by this pathogen. In addition, this pathotype exhibited diverse surface and secreted virulence factors.
A proof-of-concept sub-study exploring feasibility and preliminary evidence for the role of physical activity on neural activity during executive functioning tasks among young adults after cancer treatment
Authors: Wurz Amanda , Ayson Gladys , Smith Andra M. , Brunet Jennifer
Published: August 2021

Background

Executive functioning (EF) deficits are troubling for adolescents and young adults (AYAs) after cancer treatment. Physical activity (PA) may enhance neural activity underlying EF among older adults affected by cancer. Establishing whether PA enhances neural activity among AYAs is warranted. As part of a two-arm, mixed-methods pilot randomized controlled trial (RCT), this proof-of-concept sub-study sought to answer the following questions: (1) is it feasible to use neuroimaging with EF tasks to assess neural activity changes following a 12-week PA intervention? And (2) is there preliminary evidence that a 12-week PA intervention enhances neural activity among AYAs after cancer treatment?

Methods

AYAs in the pilot RCT were approached for enrollment into this sub-study. Those who were eligible and enrolled, completed functional magnetic resonance imaging (fMRI) with EF tasks (letter n-back, Go/No Go) pre- and post-PA intervention. Sub-study enrollment, adherence to scheduled fMRI scans, outliers, missing data, and EF task performance data were collected. Data were analyzed with descriptive statistics, blood oxygen level dependent (BOLD) analyses, and paired sample t-tests.

Results

Nine eligible participants enrolled into this sub-study; six attended scheduled fMRI scans. One outlier was identified and was subsequently removed from the analytical sample. Participants showed no differences in EF task performance from pre- to post-PA intervention. Increases in neural activity in brain regions responsible for motor control, information encoding and processing, and decision-making were observed post-PA intervention (p < 0.05; n = 5).

Conclusions

Findings  show that fMRI scans during EF tasks detected neural activity changes (as assessed by the BOLD signal) from pre- to post-PA intervention. Results thus suggest future trials confirming that PA enhances neural activity underlying EF are needed, though feasibility issues require careful consideration to ensure trial success.

Trial registration

clinicaltrials.gov, NCT03016728. Registered January 11, 2017, clinicaltrials.gov/ct2/show/NCT03016728.
Risk perceptions among high-risk pregnant women in Nepal: a qualitative study
Authors: Rajbanshi Sushma , Norhayati Mohd Noor , Nik Hazlina Nik Hussain
Published: August 2021

Background

A woman’s perception of risk affects her decisions about seeking obstetric care and following prescribed regimens of care. This study explored the perceptions of high-risk pregnancy among women with high-risk factors.

Methods

A qualitative study was conducted in the Morang district, Nepal. A phenomenological approach was used. In-depth interviews were conducted with 14 participants. Postpartum women with one risk factor for high-risk pregnancy who non-adhere to referral hospital birth were selected purposively. Thematic analysis was done to generate themes and categories.

Findings

Two main themes emerged in this study: (i) knowledge and understanding of risk and (ii) normalizing and non-acceptance of risk. The participants had inadequate knowledge of risk in pregnancy and childbirth. Their information source was their personal experiences of risk, witnessing their close relatives, and community incidents. The participants perceived pregnancy as a normal event and did not consider themselves as at risk. They tended to deny risk and perceived that everything was fine with their pregnancy.

Conclusions

The findings of this study provide a glimpse into how women perceived risk and the reasons that lead them to deny the risks and gave home birth. In the presence of risk factors in pregnancy, some women were not convinced that they were at risk. An antenatal check-up should be utilized as a platform to educate women, explore their intentions, and encourage safer births.
Alteration in the mRNA expression profile of the autophagy-related mTOR pathway in schizophrenia patients treated with olanzapine
Authors: Cui Fengwei , Gu Shuguang , Gu Yue , Yin Jiajun , Fang Chunxia , Liu Liang
Published: August 2021

Background

The mammalian target of rapamycin protein (mTOR) signaling pathway is involved in the pathogenesis of schizophrenia and the mechanism of extrapyramidal adverse reactions to antipsychotic drugs, which might be mediated by an mTOR-dependent autophagy impairment. This study aimed to examine the expression of mTOR pathway genes in patients with schizophrenia treated with olanzapine, which is considered an mTOR inhibitor and autophagy inducer.

Methods

Thirty-two patients with acute schizophrenia who had been treated with olanzapine for four weeks (average dose 14.24 ± 4.35 mg/d) and 32 healthy volunteers were recruited. Before and after olanzapine treatment, the Positive and Negative Syndrome Scale (PANSS) was used to evaluate the symptoms of patients with schizophrenia, and the mRNA expression levels of mTOR pathway-related genes, including MTOR, RICTOR, RAPTOR, and DEPTOR, were detected in fasting venous blood samples from all subjects using real-time quantitative PCR.

Results

The MTOR and RICTOR mRNA expression levels in patients with acute schizophrenia were significantly decreased compared with those of healthy controls and further significantly decreased after four weeks of olanzapine treatment. The DEPTOR mRNA expression levels in patients with acute schizophrenia were not significantly different from those of healthy controls but were significantly increased after treatment. The expression levels of the RAPTOR mRNA were not significantly different among the three groups. The pairwise correlations of MTOR, DEPTOR, RAPTOR, and RICTOR mRNA expression levels in patients with acute schizophrenia and healthy controls were significant. After olanzapine treatment, the correlations between the expression levels of the DEPTOR and MTOR mRNAs and between the DEPTOR and RICTOR mRNAs disappeared.

Conclusions

Abnormalities in the mTOR pathway, especially DEPTOR and mTORC2, might play important roles in the autophagy mechanism underlying the pathophysiology of schizophrenia and effects of olanzapine treatment.
Association between food intake and obesity in pregnant women living with and without HIV in Cape Town, South Africa: a prospective cohort study
Authors: Madlala Hlengiwe P. , Steyn Nelia P. , Kalk Emma , Davies Mary-Anne , Nyemba Dorothy , Malaba Thokozile R. , Mehta Ushma , Petro Gregory , Boulle Andrew , Myer Landon
Published: August 2021

Background

Although global nutrition/dietary transition resulting from industrialisation and urbanisation has been identified as a major contributor to widespread trends of obesity, there is limited data in pregnant women, including those living with HIV in South Africa. We examined food-based dietary intake in pregnant women with and without HIV at first antenatal care (ANC) visit, and associations with maternal overweight/obesity and gestational weight gain (GWG).

Methods

In an urban South African community, consecutive women living with (n = 479) and without (n = 510) HIV were enrolled and prospectively followed to delivery. Interviewer-administered non-quantitative food frequency questionnaire was used to assess dietary intake (starch, protein, dairy, fruits, vegetables, legumes, oils/fats) at enrolment. Associations with maternal body mass index (BMI) and GWG were examined using logistic regression models.

Results

Among women (median age 29 years, IQR 25–34), the prevalence of obesity (BMI ≥ 30 kg/m2) at first ANC was 43% and that of excessive GWG (per IOM guidelines) was 37% overall; HIV prevalence was 48%. In women without HIV, consumption of potato (any preparation) (aOR 1.98, 95% CI 1.02–3.84) and pumpkin/butternut (aOR 2.13, 95% CI 1.29–3.49) for 1–3 days a week increased the odds of overweight/obesity compared to not consuming any; milk in tea/coffee (aOR 6.04, 95% CI 1.37–26.50) increased the odds of excessive GWG. Consumption of eggs (any) (aOR 0.52, 95% CI 0.32–0.86) for 1–3 days a week reduced the odds of overweight/obesity while peanut and nuts consumption for 4–7 days a week reduced the odds (aOR 0.34, 95% CI 0.14–0.80) of excessive GWG.

In women with HIV, consumption of milk/yoghurt/maas to drink/on cereals (aOR 0.35, 95% CI 0.18–0.68), tomato (raw/cooked) (aOR 0.50, 95% CI 0.30–0.84), green beans (aOR 0.41, 95% CI 0.20–0.86), mixed vegetables (aOR 0.49, 95% CI 0.29–0.84) and legumes e.g. baked beans, lentils (aOR 0.50, 95% CI 0.28–0.86) for 4–7 days a week reduced the odds of overweight/obesity; tomato (raw/cooked) (aOR 0.48, 95% CI 0.24–0.96) and mixed vegetables (aOR 0.38, 95% CI 0.18–0.78) also reduced the odds of excessive GWG.

Conclusions

Diet modification may promote healthy weight in pregnant women living with and without HIV.
Fertility sparing surgery in malignant ovarian Germ cell tumor (MOGCT): 15 years experiences
Authors: Zamani Narges , Rezaei Poor Mohadese , Ghasemian Dizajmehr Sedigheh , Alizadeh Shima , Modares Gilani Mitra
Published: August 2021

Aim

We aim to evaluate the reproductive outcome of fertility-sparing surgery and chemotherapy among young women diagnosed with MOGCT of any stage.

Methods

In the current retrospective study we evaluated 79 patients with malignant ovarian germ cell tumors (MOGCT) who visited at Imam Center, Vali-e-asr Hospital, Gynecologic Oncology department during 2001–2016. Reproductive outcomes (menstruation status and childbearing) followed fertility-preserving surgery and adjuvant chemotherapy by filling questionnaires. Statistical analysis was done with SPSS software, Chi-Square Tests were done, and significance was determined at P ≤ 0.05. Results among 79 young women who underwent fertility-sparing treatment, 72 patients followed up for reproductive outcome, and 7 patients excluded because of death (3 cases), XY genotyping (3 cases), and bilateral ovarian involvement (1 case). The mean age at presentation was 23 years. (Range: 19–33 years). The 5 and 10-year disease-free survival rate was 87% and 94.4%, respectively. The overall survival rate (OSR) was 94.4% at 5 and 10 years. Regular menstruation recovered in 60 of 72 patients after treatment (83%). All patients without adjuvant chemotherapy experienced regular menstruation, while normal menstruation was retrieved in 78% in the adjuvant chemotherapy group at the end of treatment. This retrieval of regular menstruation was not dependent on the age or number of chemotherapy cycles. 19 of 26 patients who attempted pregnancy were led to delivery (73%). No one required infertility treatments. The mean of chemotherapy cycles is related to a successful pregnancy.

Conclusion

We showed patients with MOGCT could become pregnant and give birth if they desire. The advanced tumor stage wasn't the convincing factor for avoiding fertility preservation. Fertility sparing surgery with adjuvant chemotherapy is a safe treatment and results in a high fertility rate.
Improving access to medicines for non-communicable diseases in rural primary care: results from a quasi-randomized cluster trial in a district in South India
Authors: Pati Manoj Kumar , Bhojani Upendra , Elias Maya Annie , Srinivas Prashanth N.
Published: August 2021

Background

A large proportion of non-communicable diseases (NCDs) are treatable within primary health care (PHC) settings in a cost-effective manner. However, the utilization of PHCs for NCD care is comparatively low in India. The Access-to-Medicines (ATM) study examined whether (and how) interventions aimed at health service optimization alone or combined with community platform strengthening improve access to medicines at the primary health care level within the context of a local health system.

Method

A quasi-randomized cluster trial was used to assess the effectiveness of the intervention (18 months) implemented across 39 rural PHCs (clusters) of three sub-districts of Tumkur in southern India. The intervention was allocated randomly in a 1:1:1 sequence across PHCs and consisted of three arms: Arm A with a package of interventions aimed at health service delivery optimization; B for strengthening community platforms in addition to A; and the control arm. Group allocation was not blinded to providers and those who assessed outcomes. A household survey was used to understand health-seeking behaviour, access and out-of-pocket expenditure (OOP) on key anti-diabetic and anti-hypertension medicines among patients; facility surveys were used to assess the availability of medicines at PHCs. Primary outcomes of the study are the mean number of days of availability of antidiabetic and antihypertensive medicines at PHCs, the mean number of patients obtaining medicines from PHC and OOP expenses.

Result

The difference-in-difference estimate shows a statistically insignificant increase of 31.5 and 11.9 in mean days for diabetes and hypertension medicines availability respectively in the study arm A PHCs beyond the increase in the control arm. We further found that there was a statistically insignificant increase of 2.2 and 3.8 percentage points in the mean proportion of patients obtaining medicines from PHC in arm A and arm B respectively, beyond the increase in the control arm.

Conclusion

There were improvements in NCD medicine availability across PHCs, the number of patients accessing PHCs and reduction in OOP expenditure among patients, across the study arms as compared to the control arm; however, these differences were not statistically significant.

Trial registration

Trial registration number CTRI/2015/03/005640. This trial was registered on 17/03/2015 in the Clinical Trial Registry of India (CTRI) after PHCs were enrolled in the study (retrospectively registered). The CTRI is the nodal agency of the Indian Council of Medical Research for registration of all clinical, experimental, field intervention and observation studies.
A novel compound heterozygous variant of the SLC12A3 gene in Gitelman syndrome with diabetes and the choices of the appropriate hypoglycemic drugs: a case report
Authors: Liu Zhiying , Wang Sai , Zhang Ruixiao , Wang Cui , Lu Jingru , Shao Leping
Published: August 2021

Background

Gitelman syndrome (GS) is an autosomal recessive tubulopathy caused by mutations of the SLC12A3 gene. It is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. It is universally known that both hypokalemia and hypomagnesemia can influence insulin secretion and insulin resistance, but the exact mechanisms require further study. We identified a novel deletion variant of the SLC12A3 gene and discussed the appropriate hypoglycemic drugs in Gitelman syndrome (GS) patients with type 2 diabetes.

Case presentation

A 55-year-old diabetic female patient was hospitalized for evaluation because of paroxysmal general weakness and numbness of extremities for one year. We suspected that she was suffering from GS by initial estimation. Direct Sanger sequencing was used to analyze the causative gene SLC12A3 of GS. Oral glucose tolerance test (OGTT) was carried out to assess the glucose metabolism and insulin resistance status. Genetic analysis revealed that she was a compound heterozygote for a recurrent missense mutation c.179C > T and a novel deletion c.1740delC in SLC12A3, thus her diagnosis of GS was confirmed. The patient was treated with potassium chloride (3.0 g/d) and magnesium chloride (element magnesium 350 mg/d) on the basis of initial treatment of diabetes with hypoglycemic drug (Repaglinide, 3.0 mg/day). However, she developed frequent hypoglycemia after one week. OGTT showed that her glucose metabolism and insulin resistance much improved after potassium and magnesium supplemental therapy. Then we changed the hypoglycemic agent to a dipeptidyl peptidase-4 (DPP-4) inhibitor (Trajenta 5 mg/d), since then her blood glucose level remained normal during two-year of follow-up.

Conclusion

We have identified a novel deletion of the SLC12A3 gene and discussed the appropriate hypoglycemic drugs in Gitelman syndrome (GS) patients with type 2 diabetes. We suggested that attention need to be paid to blood glucose monitoring in GS patients, especially when hypokalemia and hypomagnesemia are corrected. Besides, the insufficient blood volume and serum electrolyte disturbance should also be taken into consideration in the selecting hypoglycemic drugs for GS patients.
Development and optimization of a microbial co-culture system for heterologous indigo biosynthesis
Authors: Chen Tingting , Wang Xiaonan , Zhuang Lei , Shao Alan , Lu Yinghua , Zhang Haoran
Published: August 2021

Background

Indigo is a color molecule with a long history of being used as a textile dye. The conventional production methods are facing increasing economy, sustainability and environmental challenges. Therefore, developing a green synthesis method converting renewable feedstocks to indigo using engineered microbes is of great research and application interest. However, the efficiency of the indigo microbial biosynthesis is still low and needs to be improved by proper metabolic engineering strategies.

Results

In the present study, we adopted several metabolic engineering strategies to establish an efficient microbial biosynthesis system for converting renewable carbon substrates to indigo. First, a microbial co-culture was developed using two individually engineered E. coli strains to accommodate the indigo biosynthesis pathway, and the balancing of the overall pathway was achieved by manipulating the ratio of co-culture strains harboring different pathway modules. Through carbon source optimization and application of biosensor-assisted cell selection circuit, the indigo production was improved significantly. In addition, the global transcription machinery engineering (gTME) approach was utilized to establish a high-performance co-culture variant to further enhance the indigo production. Through the step-wise modification of the established system, the indigo bioproduction reached 104.3 mg/L, which was 11.4-fold higher than the parental indigo producing strain.

Conclusion

This work combines modular co-culture engineering, biosensing, and gTME for addressing the challenges of the indigo biosynthesis, which has not been explored before. The findings of this study confirm the effectiveness of the developed approach and offer a new perspective for efficient indigo bioproduction. More broadly, this innovative approach has the potential for wider application in future studies of other valuable biochemicals’ biosynthesis.
Characterization of three glutamate decarboxylases from Bacillus spp. for efficient γ-aminobutyric acid production
Authors: Sun Lei , Bai Yingguo , Zhang Xiu , Zhou Cheng , Zhang Jie , Su Xiaoyun , Luo Huiying , Yao Bin , Wang Yuan , Tu Tao
Published: August 2021

Background

Gamma-aminobutyric acid (GABA) is an important bio-product used in pharmaceuticals and functional foods and as a precursor of the biodegradable plastic polyamide 4. Glutamate decarboxylase (GAD) converts l-glutamate (l-Glu) into GABA via decarboxylation. Compared with other methods, develop a bioconversion platform to produce GABA is of considerable interest for industrial use.

Results

Three GAD genes were identified from three Bacillus strains and heterologously expressed in Escherichia coli BL21 (DE3). The optimal reaction temperature and pH values for three enzymes were 40 °C and 5.0, respectively. Of the GADs, GADZ11 had the highest catalytic efficiency towards l-Glu (2.19 mM− 1 s− 1). The engineered E. coli strain that expressed GADZ11 was used as a whole-cell biocatalyst for the production of GABA. After repeated use 14 times, the cells produced GABA with an average molar conversion rate of 98.6% within 14 h.

Conclusions

Three recombinant GADs from Bacillus strains have been conducted functional identification. The engineered E. coli strain heterologous expressing GADZ1, GADZ11, and GADZ20 could accomplish the biosynthesis of l-Glu to GABA in a buffer-free reaction at a high l-Glu concentration. The novel engineered E. coli strain has the potential to be a cost-effective biotransformation platform for the industrial production of GABA.
CircFAM13B promotes the proliferation of hepatocellular carcinoma by sponging miR-212, upregulating E2F5 expression and activating the P53 pathway
Authors: Xie Ying , Hang Xiaofeng , Xu Wensheng , Gu Jing , Zhang Yuanjing , Wang Jianrong , Zhang Xiucui , Cao Xinghao , Zhan Junjie , Wang Junxue , Gan Jianhe
Published: August 2021

Background

Most of the biological functions of circular RNAs (circRNAs) and the potential underlying mechanisms in hepatocellular carcinoma (HCC) have not yet been discovered.

Methods

In this study, using circRNA expression data from HCC tumor tissues and adjacent tissues from the Gene Expression Omnibus database, we identified out differentially expressed circRNAs and verified them by qRT-PCT. Functional experiments were performed to evaluate the effects of circFAM13B in HCC in vitro and in vivo.

Results

We found that circFAM13B was the most significantly differentially expressed circRNA in HCC tissue. Subsequently, in vitro and in vivo studies also demonstrated that circFAM13B promoted the proliferation of HCC. Further studies revealed that circFAM13B, a sponge of miR-212, is involved in the regulation of E2F5 gene expression by competitively binding to miR-212, inhibits the activation of the P53 signalling pathway, and promotes the proliferation of HCC cells.

Conclusions

Our findings revealed the mechanism underlying the regulatory role played by circFAM13B, miR-212 and E2F5 in HCC. This study provides a new theoretical basis and novel target for the clinical prevention and treatment of HCC.
Coverage, determinants of use and repurposing of long-lasting insecticidal nets two years after a mass distribution in Lihir Islands, Papua New Guinea: a cross-sectional study
Authors: Millat-Martínez Pere , Gabong Rebecca , Balanza Núria , Luana Sakaia , Sanz Sergi , Raulo Silvia , Elizah Arthur , Wali Chilaka , Paivu Benjamin , Dalmas Julian , Tabie Samson , Karl Stephan , Laman Moses , Pomat William , Mitjà Oriol , Baro Bàrbara , Bassat Quique
Published: August 2021

Background

Universal coverage with long-lasting insecticidal nets (LLINs) is an essential component of malaria control programmes. Three-yearly mass distribution of LLINs in Papua New Guinea (PNG) has been successful in reducing infection transmission since 2009, but malaria prevalence ramped up from 2015 onwards. Although LLIN universal coverage is mostly achieved during these campaigns, it may not be related with net use over time. Uses given to LLINs and non-compliance of this strategy were evaluated.

Methods

A knowledge, attitude and practice (KAP) cross-sectional study was conducted in Lihir Islands, PNG, 2–2.5 years after the last LLIN mass distribution campaign. Data on bed net ownership, use and maintenance behaviour was collected using a household questionnaire administered by trained community volunteers. Logistic regression models were used to identify factors associated with owning at least one LLIN and sleeping under a LLIN the previous night.

Results

Among 2694 households surveyed, 27.4 % (95 % CI: 25.8–29.2) owned at least one LLIN and 8.7 % (95 % CI: 7.6–9.8) had an adequate LLIN coverage (at least one LLIN for every two people). Out of 13,595 individuals in the surveyed households, 13.6 % (95 % CI: 13.0-–4.2) reported having slept under a LLIN the preceding night. Determinants for sleeping under LLIN included living in a household with adequate LLIN coverage [adjusted OR (aOR) = 5.82 (95 % CI: 3.23–10.49)], household heads knowledge about LLINs [aOR = 16.44 (95 % CI: 8.29–32.58)], and female gender [aOR = 1.92 (95 % CI: 1.53–2.40)] (all p-values < 0.001). LLIN use decreased with older age [aOR = 0.29 (95 % CI: 0.21–0.40) for ≥ 15 year-olds, aOR = 0.38 (95 % CI: 0.27–0.55) for 5–14 year-olds] compared to < 5 year-olds (p-value < 0.001). Knowledge on the use of LLIN was good in 37.0 % of the household heads. Repurposed nets were reported serving as fishing nets (30.4 %), fruits and seedlings protection (26.6 %), covering up food (19.0 %) and bed linen (11.5 %).

Conclusions

Two years after mass distribution, LLIN coverage and use in Lihir Islands is extremely low. Three yearly distribution campaigns may not suffice to maintain an acceptable LLIN coverage unless knowledge on maintenance and use is promoted trough educational campaigns.
Thymoquinone loading into hydroxyapatite/alginate scaffolds accelerated the osteogenic differentiation of the mesenchymal stem cells
Authors: Rahmani-Moghadam Ebrahim , Talaei-Khozani Tahereh , Zarrin Vahideh , Vojdani Zahra
Published: August 2021

Background

Phytochemical agents such as thymoquinone (TQ) have osteogenic property. This study aimed to investigate the synergic impact of TQ and hydroxyapatite on mesenchymal stem cell differentiation. Alginate was also used as drug vehicle.

Methods

HA scaffolds were fabricated by casting into polyurethane foam and sintering at 800 °C, and then, 1250 °C and impregnated by TQ containing alginate. The adipose-derived stem cells were aliquoted into 4 groups: control, osteogenic induced-, TQ and osteogenic induced- and TQ-treated cultures. Adipose derived-mesenchymal stem cells were mixed with alginate and loaded into the scaffolds

Results

The results showed that impregnation of HA scaffold with alginate decelerated the degradation rate and reinforced the mechanical strength. TQ loading in alginate/HA had no significant influence on physical and mechanical properties. Real-time RT-PCR showed significant elevation in collagen, osteopontin, and osteocalcin expression at early phase of differentiation. TQ also led to an increase in alkaline phosphatase activity. At long term, TQ administration had no impact on calcium deposition and proliferation rate as well as bone-marker expression.

Conclusion

TQ accelerates the differentiation of the stem cells into the osteoblasts, without changing the physical and mechanical properties of the scaffolds. TQ also showed a synergic influence on differentiation potential of mesenchymal stem cells.
Improving the ameliorative effects of berberine and curcumin combination via dextran-coated bilosomes on non-alcohol fatty liver disease in mice
Authors: Chen Yi , Jiang Zhaohui , Xu Jinzhuan , Zhang Jiyuan , Sun Runbin , Zhou Jia , Lu Yuan , Gong Zipeng , Huang Jing , Shen Xiangchun , Du Qianming , Peng Jianqing
Published: August 2021

Background

The combination of berberine (BER) and curcumin (CUR) has been verified with ameliorative effects on non-alcohol fatty liver disease (NAFLD). However, discrepant bioavailability and biodistribution of BER and CUR remained an obstacle to achieve synergistic effects. Multilayer nanovesicles have great potential for the protection and oral delivery of drug combinations. Therein lies bile salts inserted liposomes, named as bilosomes, that possesses long residence time in the gastrointestinal tract (GIT) and permeability across the small intestine. Diethylaminoethyl dextran (DEAE-DEX) is generally used as an outside layer on the nanovesicles to increase the mucinous stability and promote oral absorption. Herein, we developed a DEAE-DEX-coated bilosome with BER and CUR encapsulated (DEAE-DEX@LSDBC) for the treatment of NAFLD.

Results

DEAE-DEX@LSDBC with 150 nm size exhibited enhanced permeation across mucus and Caco-2 monolayer. In vivo pharmacokinetics study demonstrated that DEAE-DEX@LSDBC profoundly prolonged the circulation time and improved the oral absorption of both BER and CUR. Intriguingly, synchronized biodistribution of BER and CUR and highest biodistribution at liver was achieved by DEAE-DEX@LSDBC, which contributed to the optimal ameliorative effects on NAFLD. It was further verified to be mainly mediated by anti-oxidation and anti-inflammation related pathways

Conclusion

DEAE-DEX coated bilosome displayed promoted oral absorption, prolonged circulation and synchronized biodistribution of BER and CUR, leading to improved ameliorative effects on NAFLD in mice, which provided a promising strategy for oral administration of drug combinations.

Graphic abstract
Plasma heat shock protein 90alpha as a biomarker for the diagnosis of liver cancer: in patients with different clinicopathologic characteristics
Authors: Han Yueting , Zhang Youqin , Cui Lin , Li Ze , Feng Honglei , Zhang Ying , Sun Da , Ren Li
Published: August 2021

Purposes

The purposes of this study were to assess the correlation between the plasma level of Hsp90α and the clinicopathological characteristics of patients with liver cancer and compare the diagnostic efficacy of Hsp90α, AFP, CEA, and CA199 in HCC.

Experimental design

A total of 200 individuals, including 140 patients with liver cancer or benign liver diseases and 60 healthy people, were enrolled for quantitative measurement of plasma Hsp90α by ELISA.

Results

The plasma level of Hsp90α was significantly different between patients with liver cancer or benign liver diseases and healthy controls (P < 0.001). The sensitivity, specificity, and AUC (95% CI) of Hsp90α were 93.2%, 85.4%, and 0.931% (0.891–0.972%), respectively, when Hsp90α was applied to differentiate liver cancer patients and healthy controls. Significant positive correlations between the plasma Hsp90α level and clinicopathological characteristics such as the history of basic liver disease (P = 0.038), active stage of hepatitis (P = 0.039), Child-Pugh score (P < 0.001), size of focal liver lesions (P = 0.004), and extrahepatic metastasis (P < 0.001) were observed. AFP + Hsp90α was the best combination strategy for the auxiliary diagnosis of HCC, with a sensitivity of 95.7%, a specificity of 97.5%, and an AUC of 0.990 (0.976–1.000). The level of plasma Hsp90α decreased significantly (P < 0.001) after resection of tumor tissue.

Conclusions

This study demonstrated that plasma Hsp90α levels are useful as a diagnostic biomarker in liver cancer and may predict the responses of patients with liver cancer to surgery. Some clinicopathological characteristics could affect the plasma Hsp90α levels.
Participation of women in the health workforce in the fragile and conflict-affected countries: a scoping review
Authors: Ayaz Basnama , Martimianakis Maria Athina , Muntaner Carles , Nelson Sioban
Published: August 2021

Introduction and background

The full participation of women as healthcare providers is recognized globally as critical to favorable outcomes at all levels, including the healthcare system, to achieving universal health coverage and sustainable development goals (SDGs) by 2030. However, systemic challenges, gender biases, and inequities exist for women in the global healthcare workforce. Fragile and conflict-affected states/countries (FCASs) experience additional pressures that require specific attention to overcome challenges and disparities for sustainable development. FCASs account for 42% of global deaths due to communicable, maternal, perinatal, and nutritional conditions, requiring an appropriate health workforce. Consequently, there is a need to understand the impact of gender on workforce participation, particularly women in FCASs.

Methods

This scoping review examined the extent and nature of existing literature, as well as identified factors affecting women's participation in the health workforce in FCASs. Following Arksey and O'Malley's scoping review methodology framework, a systematic search was conducted of published literature in five health sciences databases and grey literature. Two reviewers independently screened the title and abstract, followed by a full-text review for shortlisted sources against set criteria.

Results

Of 4284, 34 sources were reviewed for full text, including 18 primary studies, five review papers, and 11 grey literature sources. In most FCASs, women predominate in the health workforce, concentrated in nursing and midwifery professions; medicine, and the decision-making and leadership positions, however, are occupied by men. The review identified several constraints for women, related to professional hierarchies, gendered socio-cultural norms, and security conditions. Several sources highlight the post-conflict period as a window of opportunity to break down gender biases and stereotypes, while others highlight drawbacks, including influences by consultants, donors, and non-governmental organizations. Consultants and donors focus narrowly on programs and interventions solely serving women's reproductive health rather than taking a comprehensive approach to gender mainstreaming in planning human resources during the healthcare system’s restructuring.

Conclusion

The review identified multiple challenges and constraints facing efforts to create gender equity in the health workforce of FCASs. However, without equal participation of women in the health workforce, it will be difficult for FCASs to make progress towards achieving the SDG on gender equality.
Task-sharing to support paediatric and child health service delivery in low- and middle-income countries: current practice and a scoping review of emerging opportunities
Authors: Zhao Yingxi , Hagel Christiane , Tweheyo Raymond , Sirili Nathanael , Gathara David , English Mike
Published: August 2021

Background

Demographic and epidemiological changes have prompted thinking on the need to broaden the child health agenda to include care for complex and chronic conditions in the 0–19 years (paediatric) age range. Providing such services will be undermined by general and skilled paediatric workforce shortages especially in low- and middle-income countries (LMICs). In this paper, we aim to understand existing, sanctioned forms of task-sharing to support the delivery of care for more complex and chronic paediatric and child health conditions in LMICs and emerging opportunities for task-sharing. We specifically focus on conditions other than acute infectious diseases and malnutrition that are historically shifted.

Methods

We (1) reviewed the Global Burden of Diseases study to understand which conditions may need to be prioritized; (2) investigated training opportunities and national policies related to task-sharing (current practice) in five purposefully selected African countries (Kenya, Uganda, Tanzania, Malawi and South Africa); and (3) summarized reported experience of task-sharing and paediatric and child health service delivery through a scoping review of research literature in LMICs published between 1990 and 2019 using MEDLINE, Embase, Global Health, PsycINFO, CINAHL and the Cochrane Library.

Results

We found that while some training opportunities nominally support emerging roles for non-physician clinicians and nurses, formal scopes of practices often remain rather restricted and neither training nor policy seems well aligned with probable needs from high-burden complex and chronic conditions. From 83 studies in 24 LMICs, and aside from the historically shifted conditions, we found some evidence examining task-sharing for a small set of specific conditions (circumcision, some complex surgery, rheumatic heart diseases, epilepsy, mental health).

Conclusion

As child health strategies are further redesigned to address the previously unmet needs careful strategic thinking on the development of an appropriate paediatric workforce is needed. To achieve coverage at scale countries may need to transform their paediatric workforce including possible new roles for non-physician cadres to support safe, accessible and high-quality care.
The pragmatic, rapid, and iterative dissemination and implementation (PRIDI) cycle: adapting to the dynamic nature of public health emergencies (and beyond)
Authors: Yousefi Nooraie Reza , Shelton Rachel C. , Fiscella Kevin , Kwan Bethany M. , McMahon James M.
Published: August 2021

Background

Public health emergencies—such as the 2020 COVID-19 pandemic—accelerate the need for both evidence generation and rapid dissemination and implementation (D&I) of evidence where it is most needed. In this paper, we reflect on how D&I frameworks and methods can be pragmatic (i.e., relevant to real-world context) tools for rapid and iterative planning, implementation, evaluation, and dissemination of evidence to address public health emergencies.

The pragmatic, rapid, and iterative D&I (PRIDI) cycle

The PRIDI cycle is based on a “double-loop” learning process that recognizes the need for responsiveness and iterative adaptation of implementation cycle (inner loop) to the moving landscapes, presented by the outer loops of emerging goals and desired outcomes, emerging interventions and D&I strategies, evolving evidence, and emerging characteristics and needs of individuals and contexts. Stakeholders iteratively evaluate these surrounding landscapes of implementation, and reconsider implementation plans and activities.

Conclusion

Even when the health system priority is provision of the best care to the individuals in need, and scientists are focused on development of effective diagnostic and therapeutic technologies, planning for D&I is critical. Without a flexible and adaptive process of D&I, which is responsive to emerging evidence generation cycles, and closely connected to the needs and priorities of stakeholders and target users through engagement and feedback, the interventions to mitigate public health emergencies (e.g., COVID-19 pandemic), and other emerging issues, will have limited reach and impact on populations that would most benefit. The PRIDI cycle is intended to provide a pragmatic approach to support planning for D&I throughout the evidence generation and usage processes.