bluuebunny/crossref_metadata_2025 huggingface dataset:
PolyHaplotyper: haplotyping in polyploids based on bi-allelic marker dosage data
Authors: Voorrips Roeland E. , Tumino Giorgio
Published: October 2022

Background

For genetic analyses, multi-allelic markers have an advantage over bi-allelic markers like SNPs (single nucleotide polymorphisms) in that they carry more information about the genetic constitution of individuals. This is especially the case in polyploids, where individuals carry more than two alleles at each locus. Haploblocks are multi-allelic markers that can be derived by phasing sets of closely-linked SNP markers. Phased haploblocks, similarly to other multi-allelic markers, will therefore be advantageous in genetic tasks like linkage mapping, QTL mapping and genome-wide association studies.

Results

We present a new method to reconstruct haplotypes from SNP dosages derived from genotyping arrays, which is applicable to polyploids. This method is implemented in the software package PolyHaplotyper. In contrast to existing packages for polyploids it makes use of full-sib families among the samples to guide the haplotyping process. We show that in this situation it is much more accurate than other available software, using experimental hexaploid data and simulated tetraploid data.

Conclusions

Our method and the software package PolyHaplotyper in which it is implemented extend the available tools for haplotyping in polyploids. They perform especially well in situations where one or more full-sib families are present.
EchinoDB: an update to the web-based application for genomic and transcriptomic data on echinoderms
Authors: Mittal Varnika , Reid Robert W. , Machado Denis Jacob , Mashanov Vladimir , Janies Daniel A.
Published: October 2022

Background

Here we release a new version of EchinoDB, EchinoDB v2.0 (https://echinodb.uncc.edu). EchinoDB is a database of genomic and transcriptomic data on echinoderms. The initial database consisted of groups of 749,397 orthologous and paralogous transcripts arranged in orthoclusters by sequence similarity.

Results

The updated version of EchinoDB includes two new major datasets: the RNA-Seq data of the brittle star Ophioderma brevispinum and the high-quality genomic assembly data of the green sea urchin Lytechinus variegatus. In addition, we enabled keyword searches for annotated data and installed an updated version of Sequenceserver to allow Basic Local Alignment Search Tool (BLAST) searches. The data are downloadable in FASTA format. The first version of EchinoDB appeared in 2016 and was implemented in GO on a local server. The new version has been updated using R Shiny to include new features and improvements in the application. Furthermore, EchinoDB now runs entirely in the cloud for increased reliability and scaling.

Conclusion

EchinoDB serves a user base drawn from the fields of phylogenetics, developmental biology, genomics, physiology, neurobiology, and regeneration. As use cases, we illustrate the function of EchinoDB in retrieving components of signaling pathways involved in the tissue regeneration process of different echinoderms, including the emerging model species Ophioderma brevispinum. Moreover, we use EchinoDB to shed light on the conservation of the molecular components involved in two echinoderm-specific phenomena: spicule matrix proteins involved in the formation of stereom endoskeleton and the tensilin protein that contributes to the capacity of the connective tissues to quickly change its mechanical properties. The genes involved in the former had been previously studied in echinoids, while gene sequences involved in the latter had been previously described in holothuroids. Specifically, we ask (a) if the biomineralization-related proteins previously reported only in sea urchins are also present in other, non-echinoid, echinoderms and (b) if tensilin, the protein responsible for the control of stiffness of the mutable collagenous tissue, previously described in sea cucumbers, is conserved across the phylum.
Study design of an interdisciplinary and participatory nature-based palliative rehabilitation intervention in a Danish nursing home for people with severe dementia
Authors: Schmidt Tanja , Gramkow Marie Christoffersen , Poulsen Dorthe Varning , Miller Louise Holm , Wermuth Lene , Stigsdotter Ulrika K.
Published: October 2022

Background

A limited amount of research has examined how nature-based palliative rehabilitation can be implemented in nursing homes for people with dementia, even though evidence suggests that these gardens are underused. This paper will present the study protocol of an intervention study co-designed in an interdisciplinary collaboration with a nursing home for people with dementia, to develop a tailored nature-based palliative rehabilitation program to increase qualified use of garden with the purpose of promoting a range of health outcomes.

Methods

The study is a single-cased quasi-experimental mixed methods study. The intervention will be developed, designed, and implemented in collaboration with the nursing home, using different co-design tools and methods. The effect of the intervention will be evaluated using the The Neuropsychiatric Inventory Nursing Home version in combination with medication use, a survey on staff burnout, and cameras in the garden to register garden use. A process evaluation with single- and focus group interviews consisting of various stakeholders in the study will be used to gain knowledge on the intervention processes and implementation.

Discussion

The paper presents new approaches in the field of palliative rehabilitation for people with dementia using nursing home gardens, through interdisciplinary collaboration, participatory co-design approach and mixed methods design. Using both effect and process evaluation, the study will provide unique insights in the role and importance of participatory process, interdisciplinary collaboration, and tailoring palliative rehabilitation activities in gardens at nursing homes to local needs and wishes. These results can be used to guide other nursing homes and renewal projects in the future.

Trial registration

ISRCTN, ISRCTN14095773. Registered 15 July 2022—Retrospectively registered.
Iranian Multi-center Osteoporosis Study (IMOS), 2021–2022: the study protocol
Authors: Khalagi Kazem , Fahimfar Noushin , Hajivalizadeh Fatemeh , Sanjari Mahnaz , Mansourzadeh Mohammad Javad , Gharibzadeh Safoora , Shafiee Gita , Kamali Koorosh , Alaeddini Farshid , Farzadfar Farshad , Mohseni Samaneh , Namazi Nazli , Razi Farideh , Gorgani Kobra , Kateb Saber Katayoun , Panahi Nekoo , Heshmat Ramin , Raeisi Alireza , Larijani Bagher , Ostovar Afshin
Published: October 2022

Background

This paper presents the protocol of the 4th round of Iranian Multi-center Osteoporosis Study (IMOS), a national survey with the primary objective of estimating the prevalence of osteoporosis and sarcopenia and their risk factors in a representative sample of urban and rural populations.

Methods

The target population of the survey is all individuals ≥ 50 years in Iran. A multi-stage random sampling method has been used in the study. We stratified the 31 provinces of the country into 5 strata based on the distribution of their potential risk factors for osteoporosis and randomly selected one or two provinces from each stratum. Then, we invited 2530 people aged ≥ 50 years recruited in the 8th National Survey of None Communicable Diseases (NCD) Risk Factors (STEPs-2021) in the selected provinces to participate in IMOS. Body composition measurements including bone mineral density, muscle mass, and fat mass are measured through Dual-energy X-ray Absorptiometry (DXA) method using HOLOGIC (Discovery and Horizon) devices; and Trabecular Bone Score (TBS) is measured on the DXA scans using iNsight software. Anthropometric measurement and physical examinations are made by a trained nurses and other required information are collected through face-to-face interviews made by trained nurses. Laboratory measurements are made in a central lab. The prevalence of osteoporosis and sarcopenia will be estimated after applying sampling design, non-response, and post-stratification weights to the data.

Discussion

IMOS will provide valuable information on the prevalence and determinants of osteoporosis and sarcopenia at the national level, and the results can be used in evaluating health system interventions and policymaking in the field of musculoskeletal diseases.
Multidisciplinary management of disseminated Exophiala dermatitidis mycosis in an infant with mixed phenotype acute leukemia: a case report
Authors: Nakatani Ryo , Ashiarai Miho , Yoshihara Hiroki , Yada Keigo , Nozaki Taiki , Ushigusa Takeshi , Mori Nobuyoshi , Hasegawa Daisuke
Published: October 2022

Background

Exophiala dermatitidis is a dematiaceous fungus isolated from various environmental sources. Systemic E. dermatitidis infections can lead to fatal outcomes, and treatment has not yet been standardized. Although E. dermatitidis is also known to cause cutaneous infection, it has not been previously reported to appear as ecthyma gangrenosum (EG), an uncommon cutaneous lesion in neutropenic patients that is mainly caused by Pseudomonas aeruginosa.

Case presentation

A 2-month-old male infant with mixed-phenotype acute leukemia presented with prolonged fever unresponsive to antibacterial and antifungal agents during myelosuppression due to remission induction therapy. He also presented with skin lesions on the left wrist and left lower quadrant of the abdomen. The abdominal lesion gradually turned black and necrotic, which was consistent with the findings of the EG. E. dermatitidis was isolated from the blood, stool, wrist skin, and endotracheal aspirate. During hematopoietic recovery, consolidation in both lungs was evident. Multiagent antifungal treatment failed to eliminate E. dermatitidis from blood. In order to salvage the central venous catheter, ethanol lock therapy (ELT) was adopted, following which the blood culture became negative. The abdominal lesion that evolved as a necrotic mass connecting the small intestine and subcutaneous tissue adjacent to the skin was surgically resected. After these interventions, the general condition improved.

Conclusion

Disseminated E. dermatitidis mycosis in the neutropenic infant was successfully managed with a multidisciplinary treatment consisting of multiagent antifungal treatment, ELT, and surgery.
Hopes expressed in birth plans by women diagnosed with fetal anomalies: a qualitative study in Japan
Authors: Chiba Maki Kitazono , Horiuchi Shigeko , Ishikawa Satomi , Arimori Naoko
Published: October 2022

Background

Recent advances in prenatal screening and diagnosis have resulted in an increasing number of women receiving a diagnosis of fetal anomalies. In this study, we aimed to clarify the hopes for childbirth and parenting of women diagnosed with fetal anomalies and to suggest a family-centered care tailored for this situation in perinatal settings.

Methods

A descriptive qualitative study was performed. We recruited women diagnosed with fetal anomalies who were over 22 years old, beyond 22 weeks of gestation, and had scheduled pregnancy and delivery management at a tertiary perinatal medical center specializing in neonatal and pediatric care in a metropolitan area of Japan from April 2019 to December 2019. Women who were willing to participate received support from a midwife to create birth plans. Data were collected from the documented birth plans submitted by 24 women and analyzed using content analysis.

Results

We identified three themes of women’s hopes based on the descriptions of the submitted birth plans: (1) Hopes as women who are expecting childbirth, (2) Hopes as mothers of a baby, (3) Hopes of being involved in the family needs. Several distinctive hopes were clarified in the context of the women’s challenging situations. In describing their hopes, the women were neither overoptimistic or overstated their actual situations, nor caused embarrassment to the healthcare providers. The importance of supporting their involvement in baby matters in the way each family wants also emerged. However, several barriers to fulfilling the women’s hopes were identified including the babies’ conditions and hospital regulations against family visits or presence.

Conclusion

All three themes identified in the study provide important insights for analyzing more deeply ways of implementing a family-centered care for women diagnosed with fetal anomalies in perinatal settings. To improve women’s engagement in decision-making as a team member, women’s hopes should be treated with dignity and respect, and included in the perinatal care of women with abnormal fetuses. Further research is needed to improve the inclusion of women’s hopes in their care in clinical settings.

Trial registration

UMIN Clinical Trials Registry: UMIN000033622 (First registration date: 03/08/2018).
Evaluation of the effect of gentamicin in surgical perfusion solution on cataract postoperative endophthalmitis
Authors: Ma Wenjiang , Hou Guanghua , Wang Junfang , Liu Ting , Tian Fang
Published: October 2022

Objective

To evaluate the effect of gentamicin in surgical perfusion solution on endophthalmitis incidence after cataract surgery.

Methods

A retrospective analysis of endophthalmitis incidence was conducted in two groups of patients who underwent cataract surgery, with (Group B) or without gentamicin (Group A) in the surgical perfusion solution. Endophthalmitis incidence, the isolated pathogenic bacteria strains and their antibiotic sensitivity, and the drug-resistant genotype of the pathogens were examined.

Results

The incidence of endophthalmitis in patients of group A was 0.8‰. Thirteen pathogenic bacterial strains were isolated from the patient samples in group A, including 8 strains of Staphylococcus epidermidis, 1 Staphylococcus aureus, 1 Streptococcus pneumoniae, 1 Streptococcus bovis, 1 Enterococcus faecium and 1 Morganella sp. The incidence of endophthalmitis in group B patients was 0.2‰, which was significantly lower than that in group A (P<0.05). Five strains of pathogenic bacteria were successfully isolated, including 2 strains of Enterococcus faecium, 1 Enterococcus faecalis, 1 Staphylococcus epidermidis and 1 Staphylococcus aureus. There was no significant difference in the proportion of Staphylococcus strains in all isolated bacteria between the two groups (P > 0.05). However, the proportion of Enterococci isolated in group B samples was higher than that in group A (P < 0.05). There were more gentamicin-sensitive strains than levofloxacin-sensitive strains identified (P < 0.05). Interestingly, aminoglycoside-inactivating enzyme resistance gene was detected in Enterococcus strains.

Conclusion

Our data suggest that gentamicin-containing perfusion solution can reduce the incidence of postoperative endophthalmitis in cataract patients. However, the selective pressure imposed by gentamicin may facilitate the development of aminoglycoside-resistant Enterococcos strains.
A retrospective review of vaccine wastage and associated risk factors in the Littoral region of Cameroon during 2016–2017
Authors: Nkenyi Rene , Pak Gi Deok , Tonga Calvin , Chon Yun , Park Se Eun , Kang Sunjoo
Published: October 2022

Background

Immunization is an effective preventive health intervention. In Cameroon, the Expanded Program on Immunization (EPI) aims to vaccinate children under 5 years of age for free, but vaccination coverage has consistently remained below the national target. Vaccines are distributed based on the target population size, factoring in wastage norms. However, the vaccine wastage rate (VWR) may differ among various settings. Our study aimed to assess vaccine wastage for different site settings, seasonality, and vaccine types in comparison to vaccination coverage in order to provide comprehensive insights on vaccine wastage.

Methods

A retrospective data collection and analysis were conducted on immunization and vaccine wastage data in the Littoral Region of Cameroon during 2016 and 2017. Health districts were classified as urban or rural, seasonality was categorized as rainy or dry season, and vaccine types were grouped into liquid, lyophilized, oral, and injectable vaccines. VWRs and vaccination coverage rates (VCRs) were calculated, and the vaccine waste factor was investigated.

Results

The VWR of Bacillus Calmette-Guérin (BCG; 32.19%) was the highest, followed by measles and rubella (MR; 19.05%) and yellow fever (YF; 18.34%) among all EPI vaccines in the Littoral Region of Cameroon during 2016 and 2017. Single-dose vaccine vials exhibited lower VWRs than multi-dose vials. Dry season was associated with higher VWRs for most vaccines, although more lyophilized vaccines (BCG, MR, YF vaccines) were wasted in rainy season in 2016. The VWR was persistently higher in rural than urban health districts. The months of February and November saw a decrease in VCRs. The study found an overall negative correlation between VCR and VWR.

Conclusions

Multiple factors may cause wastage of EPI vaccines in Cameroon. Vaccination area characteristics, seasonality, types of vaccines such as multi- or single-dose, lyophilized or injectable vaccines are related to VWRs in Littoral Region. Further research on vaccine wastage and vaccination coverage across Cameroon is needed to better understand the socio-behavioral aspect of vaccine in-take that may affect the level of vaccination and vaccine wastage. Public health system strengthening is warranted to adapt more real-time monitoring of the VWR and VCR for each vaccine in the government’s immunization programs.
Addison’s disease triggered by infection with mycobacterium abscessus, but not by adrenal tuberculosis or MAC pulmonary disease, in a subject with type 2 diabetes mellitus: case report
Authors: Kaneto Hideaki , Tatsumi Fuminori , Ohnishi Mana , Iwamoto Yuichiro , Katakura Yukino , Shimoda Masashi , Nakanishi Shuhei , Kaku Kohei , Mune Tomoatsu
Published: October 2022

Background

Addison’s disease is primary adrenal dysfunction and is characterized by decrease of cortisol level and increase of adrenocorticotropic hormone (ACTH) level. It is known that infection is one of main causes of Addison’s disease. Among various infections, tuberculous infection accounts for the majority of them. Recently the number of subjects with non-tuberculous mycobacterial infection has been increased, and the infection can also bring about Addison’s disease.Mycobacterium aviumcomplex (MAC) pulmonary disease accounts for the majority of non-tuberculous mycobacterial infection.

Case presentation

An 83-year-old female was suspected of having adrenal failure in our outpatient care and hospitalized in our institution. There was pigmentation in her face, hands and legs, especially in auricle and nail beds in her hands and legs. In rapid ACTH load test (0.25 mg of 1–24 ACTH), cortisol level was not increased at all. An abdominal computed tomography (CT) showed swelling of both adrenal glands accompanied by calcification. QuantiFERON test was negative andmycobacterium tuberculosiscomplex was negative in PCR test using bronchial lung lavage fluid. These data ruled out the possibility of adrenal tuberculosis. It is known that MAC pulmonary disease accounts for the majority of non-tuberculous mycobacterial infection. In this subject, however, anti-MAC antibody was negative and MAC-related bacteria were not detected in PCR test using bronchial lung lavage fluid. These data ruled out the possibility of MAC pulmonary disease.Mycobacterium abscessus(Mab) was positive in bronchial lung lavage fluid culture. Based on these data, we diagnosed this subject with Addison’s disease triggered by infection withmycobacterium abscessus, but not by adrenal tuberculous or MAC pulmonary disease. Decreased sodium level and increased eosinophil number were normalized and appetite loss was markedly mitigated after starting hydrocortisone therapy. A chest CT which was taken about 6 months later showed drastic reduction of consolidation in the upper lobe of the left lung although calcification in the adrenal gland was still observed.

Conclusions

We should bear in mind the possibility of Addison’s disease triggered by another type of infection rather than adrenal tuberculosis or MAC pulmonary disease.
Sub-chronic oral toxicity screening of quercetin in mice
Authors: Cunningham Patrice , Patton Emma , VanderVeen Brandon N. , Unger Christian , Aladhami Ahmed , Enos Reilly T. , Madero Sarah , Chatzistamou Ioulia , Fan Daping , Murphy E. Angela , Velázquez Kandy T.
Published: October 2022

Background

Quercetin is an organic flavonoid present in several fruits and vegetables. The anti-inflammatory, antiviral, antioxidant, cardio-protective, anti-carcinogenic and neuroprotective properties demonstrated by this dietary supplement endorses it as a possible treatment for inflammatory diseases and cancer. Unfortunately, conflicting research has cast uncertainties on the toxicity of quercetin. The main purpose of this study was to determine if quercetin has any toxic properties in mice at doses that have shown efficacy in pre-clinical studies regarding cancer, cancer therapy, and their off-target effects.

Methods

A sub-chronic toxicity study of quercetin was examined in male and female CD2F1 mice. Three different doses of quercetin (62, 125, and 250 mg/kg of diet) were infused into the AIN-76A purified diet and administered to mice ad libitum for 98 days. Body weight (BW), food consumption, water intake, body composition, blood count, behavior, and metabolic phenotype were assessed at various timepoints during the course of the experiment. Tissue and organs were evaluated for gross pathological changes and plasma was used to measure alkaline phosphatase (AP), aspartate transaminase (AST), and alanine transaminase (ALT).

Results

We found that low (62 mg/kg of diet), medium (125 mg/kg of diet), and high (250 mg/kg of diet) quercetin feeding had no discernible effect on body composition, organ function, behavior or metabolism.

Conclusions

In summary, our study establishes that quercetin is safe for use in both female and male CD2F1 mice when given at ~ 12.5, 25, or 50 mg/kg of BW daily doses for 14 weeks (i.e. 98 days). Further studies will need to be conducted to determine any potential toxicity of quercetin following chronic ingestion.
Health insurance status of cross-border migrant children and the associated factors: a study in a Thai-Myanmar border area
Authors: Chamchan Chalermpol , Apipornchaisakul Kanya
Published: October 2022

Background

Although policies of Thailand for migrant health protection are inclusive for all migrant groups, due to existing constraints in practices and policy implementation, many migrant children still lack the protection. This study aimed to assess the health insurance status of children aged 0-14 whose parents were cross-border migrant workers in Thailand, and factors related to the status.

Methods

A Thai-Myanmar border area, being developed as a ‘special economic zone’ by the Thai government, was selected as a study site. With a cross-sectional research design, the study collected primary data in late 2018 by a structured questionnaire from 402 migrant households that contained 803 children. The logistic generalized estimating equation (GEE) technique was applied to examine factors associated with the children’s health insurance status. These included socio-economic factors, migration factors, and health insurance-related factors.

Results

It is found that 83.2% of the migrant children did not have health insurance. Factors associated with the health insurance status included age 12-14 years (Odds ratio (OR) 2.34; 95% confidence interval (CI) 1.23-4.46), having a birth certificate (OR 1.89, 95% CI 1.04-3.45), and plan of the family in the future to remain the child in Thailand (OR 2.37, 95% CI 1.09-5.17). The primary carer’s factors that were important health insurance-related factors included having no legal work permit (OR 4.12, 95% CI 1.88-9.06), having health insurance (OR 8.51, 95% CI 3.93-18.41), little or no ability to communicate in Thai (OR 0.31, 95% CI 0.14-0.66), and understanding the right of migrant children to purchase health insurance (OR 2.57, 95% CI 1.52-4.34).

Conclusions

The findings point to the need for every migrant child to have a birth certificate, diminishing language barriers, and providing education and motivation about the need for health insurance for migrants and their accompanying dependents, especially children. For further studies, it is suggested to include migrant health insurance supply-side factors with qualitative analyses to understand how all the factors interactively determine the health insurance status of migrant children.
Potential contribution of early endothelial progenitor cell (eEPC)-to-macrophage switching in the development of pulmonary plexogenic lesion
Authors: Shao Feng-Jin , Guo Xiao-Ling , Xu Jia-Xue , Liu Rui , Li Dan-Yue , Li Qing-Hao , Zhou Ting , Fang Cun , Tan Xun
Published: October 2022

Background

Plexiform lesions, which have a dynamic appearance in structure and cellular composition, are the histological hallmark of severe pulmonary arterial hypertension in humans. The pathogenesis of the lesion development remains largely unknown, although it may be related to local inflammation and dysfunction in early progenitor endothelial cells (eEPCs). We tested the hypothesis that eEPCs contribute to the development of plexiform lesions by differentiating into macrophages in the setting of chronic inflammation.

Methods

The eEPC markers CD133 and VEGFR-2, macrophage lineage marker mannose receptor C-type 1 (MRC1), TNFα and nuclear factor erythroid 2-related factor 2 (Nrf2) in plexiform lesions in a broiler model were determined by immunohistochemistry. eEPCs derived from peripheral blood mononuclear cells were exposed to TNFα, and macrophage differentiation and angiogenic capacity of the cells were evaluated by phagocytotic and Matrigel plug assays, respectively. The role of Nrf2 in eEPC-to-macrophage transition as well as in MRC1 expression was also evaluated. Intratracheal installation of TNFα was conducted to determine the effect of local inflammation on the formation of plexiform lesions.

Results

Cells composed of the early lesions have a typical eEPC phenotype whereas those in more mature lesions display molecular and morphological characteristics of macrophages. Increased TNFα production in plexiform lesions was observed with lesion progression. In vitro studies showed that chronic TNFα challenge directed eEPCs to macrophage differentiation accompanied by hyperactivation of Nrf2, a stress-responsive transcription factor. Nrf2 activation (Keap1 knockdown) caused a marked downregulation in CD133 but upregulation in MRC1 mRNA. Dual luciferase reporter assay demonstrated that Nrf2 binds to the promoter of MRC1 to trigger its expression. In good agreement with the in vitro observation, TNFα exposure induced macrophage differentiation of eEPCs in Matrigel plugs, resulting in reduced neovascularization of the plugs. Intratracheal installation of TNFα resulted in a significant increase in plexiform lesion density.

Conclusions

This work provides evidence suggesting that macrophage differentiation of eEPCs resulting from chronic inflammatory stimulation contributes to the development of plexiform lesions. Given the key role of Nrf2 in the phenotypic switching of eEPCs to macrophages, targeting this molecular might be beneficial for intervention of plexiform lesions.
Comparative study on antimicrobial activity of mono-rhamnolipid and di-rhamnolipid and exploration of cost-effective antimicrobial agents for agricultural applications
Authors: Zhao Feng , Wang Bingxin , Yuan Menglin , Ren Sijia
Published: October 2022

Background

Chemical pesticides have defects in crop diseases control, such as narrow antimicrobial spectrum, chemicals residue risk and harm to farmland ecosystem. Antimicrobial agents from microbial sources are highly interested in agriculture. Studies showed that rhamnolipid biosurfactants possessed certain antimicrobial activity. The structural differences in rhamnolipid inevitably affect their activities. But the antimicrobial effect of mono-rhamnolipid and di-rhamnolipid is unknown. Rhamnolipid with unique structure can be produced using specific microbial cell factory.

Results

Different types of rhamnolipid were produced from differentPseudomonas aeruginosastrains. Rha-C10-C10and Rha-Rha-C10-C10were the main homologues in the separated mono-rhamnolipid and di-rhamnolipid, respectively. Both mono-rhamnolipid and di-rhamnolipid exhibited certain antimicrobial activity against the tested microbial strains, especially the fungi and Gram-positive bacteria. But mono-rhamnolipid was superior to di-rhamnolipid, with inhibition zone diameters larger than 25 mm and inhibition rate higher than 90%. The IC50 values of mono-rhamnolipid were lower than 5 mg/L against the tested bacterium and fungus, whereas the IC50 values of di-rhamnolipid were ranged from 10 mg/L to 20 mg/L. Mono-rhamnolipid stimulated the tested strains to generate higher level of intracellular ROS. Mono-rhamnolipid exhibited better antimicrobial activity to the potential agricultural pathogens, such asAlternaria alternata,Pantoea agglomeransandCladosporiumsp. The mono-rhamnolipid crude extract of strainP.aeruginosaSGΔrhlC can replace the separated mono-rhamnolipid. After 50 times dilution, the fermentation broth of the mono-rhamnolipid producing strain SGΔrhlC exhibited equal antimicrobial effect to mono-rhamnolipid (200 mg/L). Prospects of mono-rhamnolipid were also discussed for antimicrobial applications in agriculture.

Conclusions

This work discovered that mono-rhamnolipid was superior to di-rhamnolipid on antimicrobial activity for agricultural applications. Mono-rhamnolipid is an excellent candidate for agricultural biocontrol. The knockout strainP. aeruginosaSGΔrhlC is an excellent microbial cell factory for high producing mono-rhamnolipid. Its mono-rhamnolipid crude extract and its diluted fermentation broth are cost-effective antimicrobial agents. This work provided new insights to develop green and efficient antimicrobial agents for agricultural applications.
Integrated assessment of the clinical and biological value of ferroptosis-related genes in multiple myeloma
Authors: Fu Bibo , Shao Ruonan , Wang Huizhong , Chen Guanjun , Bai Shenrui , Wang Hua
Published: October 2022

Background

Ferroptosis is an iron-dependent mode of cell death that could be induced by erastin and exert antitumor effects. However, the clinical and biological roles of ferroptosis-related gene (FRG) signature and the therapeutic value of erastin in multiple myeloma (MM) remained unknown.

Methods

Clinical and gene expression data of MM subjects were extracted from the Gene Expression Omnibus (GEO) public database. Univariable cox analysis was applied to determine FRGs related to survival and the least absolute shrinkage and selection operator (LASSO) regression analysis was used to develop a prognostic model. Prediction accuracy of the model was estimated by receiver operating characteristic (ROC) curves. Functional pathway enrichments and infiltrating immune status were also analyzed. We conducted in vitro experiments to investigate the combination therapy of erastin and doxorubicin.

Results

17 FRGs were strongly associated with patient survival and 11 genes were identified to construct the prognostic model. ROC curves indicated great predictive sensitivity and specificity of the model in all cohorts. Patients were divided into low- and high-risk groups by median risk score in each cohort and the survival of the low-risk group was significantly superior than that of the high-risk group. We also observed a close relevance between functional pathways and immune infiltration with risk scores. Moreover, we combined erastin and doxorubicin in our in vitro experiments and found synergetic antitumor effects of the two agents, and the underlying mechanism is the overgeneration of intracellular Reactive Oxygen Species (ROS).

Conclusions

We demonstrated the important value of ferroptosis in patient prognosis and as a potential antitumor target for MM.
Silver nano-reporter enables simple and ultrasensitive profiling of microRNAs on a nanoflower-like microelectrode array on glass
Authors: Gan Ying , Zhou Mingxing , Ma Huiqiang , Gong Jiameng , Fung Shan-Yu , Huang Xian , Yang Hong
Published: October 2022

MicroRNAs (miRNAs) are small non-coding RNAs with ~ 22 nucleotides, playing important roles in the post-transcriptional regulation of gene expression. The expression profiles of many miRNAs are closely related to the occurrence and progression of cancer and can be used as biomarkers for cancer diagnosis and prognosis. However, their intrinsic properties, such as short length, low abundance and high sequence homology, represent great challenges in miRNA detection of clinical samples. To overcome these challenges, we developed a simple, ultrasensitive detection platform of electrochemical miRNAs chip (e-miRchip) with a novel signal amplification strategy using silver nanoparticle reporters (AgNRs) for multiplexed, direct, electronic profiling of miRNAs. A two-step hybridization strategy was used to detect miRNAs, where the target miRNA hybridizes with a stem-loop probe to unlock the probe first, and the opened stem-loop can further hybridize with AgNRs for signaling amplification. To enhance the detection sensitivity, the gold nanoflower electrodes (GNEs) were constructed in the microaperture arrays of the e-miRchips by electroplating. With the optimal size of the GNEs, the e-miRchip showed excellent performance for miR-21 detection with a detection limit of 0.56 fM and a linear range extended from 1 fM to 10 pM. The e-miRchip also exhibited good specificity in differentiating the 3-base mismatched sequences of the target miRNA. In addition, the e-miRchip was able to directly detect miR-21 expression in the total RNA extracts or cell lysates collected from lung cancer cells and normal cells. This work demonstrated the developed e-miRchip as an efficient and promising miniaturized point-of-care diagnostic device for the early diagnosis and prognosis of cancers.

Graphical Abstract
Trajectories of 24-h movement guidelines from middle adolescence to adulthood on depression and suicidal ideation: a 22-year follow-up study
Authors: García-Hermoso Antonio , Ezzatvar Yasmin , Ramírez-Vélez Robinson , López-Gil José Francisco , Izquierdo Mikel
Published: October 2022

Background:

The 24-h movement guidelines for youth and adults recommend the specific duration of physical activity, sedentary time, and sleep duration to ensure optimal health, but little is known about its relationship to mental health indicators. The aim of the study was to explore the association between 24-h movement guidelines in adolescence and its trajectories from middle adolescence (12–17 years old) to adulthood (33–39 years old) with depression and suicidal ideation in adulthood.

Methods:

This prospective cohort study included individuals who participated in Waves I (1994–1995) and V (2016–2018) of the National Longitudinal Study of Adolescent Health (Add Health) in the United States. Physical activity, screen time and sleep duration were measured using questionnaires. Adults were categorized as having depression if they had a self-reported history of depression and/or prescription medication-use for depression in the previous four weeks. Suicidal ideation was assessed by a self-reported single question in both waves. Poisson regression analyses were used to estimate the incidence rate ratio (IRR) of depression and suicidal ideation at adulthood, according to meeting specific and combinations of 24-h movement guidelines at Wave I and its trajectories from adolescence to adulthood.

Results:

The study included 7,069 individuals (56.8% women). Adolescents who met physical activity guidelines and all three guidelines at middle adolescence had lower risk of depression (IRR = 0.84, 95%CI 0.72 to 0.98) and suicidal ideation (IRR = 0.74, 95%CI 0.55 to 0.99) at adulthood than those who did not meet any of these guidelines, respectively. Individuals who met the guidelines for screen time and all three guidelines in both adolescence and adulthood had lower risk of depression (screen time, IRR = 0.87, 95% CI 0.72 to 0.98; all three, IRR = 0.37, 95% CI 0.15 to 0.92) and suicidal ideation (screen time, IRR = 0.74, 95% CI 0.51 to 0.97; all three, IRR = 0.12, 95% CI 0.06 to 0.33) than those who never met the guidelines. Additionally, individuals who did not meet all three guidelines in adolescence but met the guidelines in adulthood had lower risk of suicidal ideation than those who never met the guidelines (IRR = 0.81, 95%CI 0.45 to 0.89).

Conclusion:

Our findings highlight the importance of promoting and maintaining adherence to the 24-h movement guidelines from middle adolescence to adulthood to prevent mental health problems. However, our findings must be interpreted carefully due to declared limitations, e.g., the self-reported assessments which are subject to sources of error and bias or that the dataset used to gauge meeting a guidelines (1994–1996) was made later (2016).
Downregulation of TUSC3 promotes EMT and hepatocellular carcinoma progression through LIPC/AKT axis
Authors: Deng Ruxia , Lu Xiansheng , Hong Chang , Cai Rui , Wang Ping , Xiong Le , Wang Xiaoyu , Chen Qiaoyu , Lin Jie
Published: October 2022

Background

Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors in the digestive tract. Tumor Suppressor Candidate 3 (TUSC3) is one subunit of the endoplasmic reticulum Oligosaccharyl transferase (OST) complex, which plays an important role in N-glycosylation during the protein folding process. However, the role of TUSC3 in the initiation and progression of HCC has not been mentioned yet. In the present study, we aim to investigate the effects of TUSC3 on the initiation and progression of HCC.

Methods

Immunohistochemical assay and qRT-PCR were used to detect the expression of TUSC3 and lipase C hepatic type (LIPC) in HCC tissue and cells. Loss-of-function and gain-of-function were applied to detect the function of TUSC3 and LIPC in vivo and in vitro. Immunofluorescence assay and co-immunoprecipitation were used to detect the relationship between TUSC3 and LPC. Western blot was applied to detect the expression of epithelial–mesenchymal transition (EMT) markers and the Akt signaling pathway.

Results

TUSC3 was aberrantly decreased in hepatocellular carcinoma tissues compared to the matched adjacent normal tissues, which resulted in bigger size of tumor (P = 0.001, Table 2), worse differentiation (P = 0.006, Table 2) and an advanced BCLC stage. Down-regulation of TUSC3 led to the enhanced proliferation and migration of hepatocellular carcinoma cells in vivo and vitro, whereas the opposite effect could be observed in the TUSC3-overexpression group. The analysis of TUSC3 microarray showed that LIPC, a glycoprotein primarily synthesized and secreted by hepatocytes, was a downstream target of TUSC3, and it negatively modulated the development of HCC. The morphological changes in HCC cells indicated that TUSC3 regulated the epithelial-mesenchymal transition (EMT). Mechanistically, TUSC3 inhibited EMT progression through the LIPC/AKT axis.

Conclusion

Down-regulation of TUSC3 promotes EMT progression by activating AKT signaling via targeting LIPC in HCC, which is probably the possible mechanism driving TUSC3-deficient hepatocellular carcinoma cells toward a malignant phenotype.
Temporal trends in the burden of non-communicable diseases in countries with the highest malaria burden, 1990–2019: Evaluating the double burden of non-communicable and communicable diseases in epidemiological transition
Authors: Li Zhuo , Shi Junyi , Li Na , Wang Minmin , Jin Yinzi , Zheng Zhi-jie
Published: October 2022

Background

Non-communicable diseases (NCDs) are rapidly increasing in sub-Saharan African countries, where 96% of global malaria deaths occur. This study aimed to investigate the disease burden of NCDs in countries with the current highest malaria mortality.

Methods

Data for this study were obtained from the Global Burden of Disease 2019 study (1990–2019). We selected the ten countries with malaria’s highest age-standardised mortality rate (ASMR) and identified and ranked the five NCDs with the highest ASMR in each country. Measures of the NCDs disease burden included ASMR, age-standardised disability-adjusted life-years (DALY), years of life lost (YLL) and years lost due to a disability (YLD). The Estimated annual percentage change (EAPC) was used to examine the trends of the NCDs disease burden from 1990 to 2019.

Results

As of 2019, the ASMR of chronic liver disease, kidney disease, diabetes mellitus, Alzheimer’s disease and other dementias, hypertensive heart disease and stroke were higher than the global average. From 1990 to 2019, the ASMR for Alzheimer’s disease and other dementias, type II diabetes mellitus, and chronic kidney disease increased by 3.0%, 10.8%, 13.3%, and the age-standardised DALY rate increased by 3.7%, 27.6%, 6.3%, and the increases tended to be in younger populations.

Conclusion

The double burden of non-communicable and communicable diseases is crippling the health systems of many sub-Saharan African countries and is often neglected. The prevention, surveillance, and control of diseases require an integrated strategy, with governments and non-government organisations aligned and supported by the global initiative.
The importance of setting and therapeutic relationships when delivering chiropractic care to those living with disadvantage
Authors: Marthick-Hone Dan , Doyle Aunty Kerrie , Kennedy Gerard A. , Vindigni Dein , Polus Barbara I.
Published: October 2022

Background

Chiropractic is a mostly privatised health profession within Australia, with people experiencing disadvantage typically having limited access due to financial barriers. However, some universities within Australia offer community outreach clinics where students provide chiropractic care to people living with disadvantage. This demographic experiences higher rates of chronic conditions including musculoskeletal complaints and requires subsidisation to access privatised care. This need also offers opportunity for the chiropractic profession to work within community healthcare teams. A mixed-methods observational study was used to investigate how the unique setting of a student chiropractic community clinic may influence the experience and outcomes of those who attend.

Methods

Three patient-reported outcome measures (PROMs) investigated client outcomes: Measure Yourself Medical Outcome Profile (MYMOP); European Five Domain Five Level Quality of Life Questionnaire (EQ-5D-5L); and the Patient Enablement Instrument. The PROMs data were analysed descriptively and inferentially. Interviews were conducted with clients who had received chiropractic care, chiropractic students, clinical supervisors and staff of the centre. Interview data were coded using thematic analysis, and themes were formed using Bronfenbrenner’s socio-ecological systems framework and non-participant observations.

Results

Thirty-seven participants completed baseline PROMs and 17 completed follow-ups after four treatments. Seventy-two percent of participants nominated their primary complaint as chronic. Significant change was noted in general health and wellbeing for the MYMOP, pain and disability for the EQ-5D-5L and index scores for the EQ-5D-5L suggested improved health and wellbeing. Most clients experienced higher levels of enablement post treatment. Twelve participants were interviewed (four were clients), with five themes emerging from the interview data. Clients reported their lived experiences impacted their health problems and attending the clinic offered benefits beyond improvement of pain and disability.

Conclusions

Interview data suggested that these benefits were due to a combination of therapy, the setting and the relationships formed within that setting. Complementing this, PROM data suggested clients experienced better levels of health and wellbeing and decreased levels of pain and disability. Findings indicated that people who experienced disadvantage may receive broader benefits from attending community centres offering chiropractic care. Services such as chiropractic may be complementary in meeting the healthcare needs of those experiencing disadvantage.
LncRNA PCED1B-AS1 knockdown inhibits osteosarcoma via methylation-mediated miR-10a downregulation
Authors: Wang Bing , Yao Li , Dong Yuefu , Liu Jian , Wu Jian
Published: October 2022

Background

LncRNA PCED1B-AS1 (PCED1B-AS1) promotes glioma. This study aimed to investigate its role in osteosarcoma (OS).

Methods

The study included 60 OS patients. Accumulation of miR-10a and PCED1B-AS1 in tissues from OS patients and cell lines was determined by RT-qPCR. Cell transfections were performed for interaction analysis. Participation of PCED1B-AS1 siRNA silencing and miR-10a overexpression in proliferation, invasion, and migration of U2OS and MG-63 cells was analyzed by cell proliferation assay and Transwell assay.

Results

PCED1B-AS1 level was increased in OS and positively correlated with miR-10a level. In OS cells, PCED1B-AS1 siRNA silencing downregulated miR-10a. Methylation-specific PCR analysis showed that PCED1B-AS1 siRNA silencing decreased the methylation of miR-10a gene promoter. Moreover, PCED1B-AS1 siRNA silencing suppressed OS cell proliferation, invasion, and migration. In addition, miR-10a overexpression attenuated the effects of PCED1B-AS1 siRNA silencing.

Conclusion

PCED1B-AS1 knockdown may inhibit OS cell proliferation and movement by regulating miR-10 gene methylation.
Combination of curcumin and piperine synergistically improves pain-like behaviors in mouse models of pain with no potential CNS side effects
Authors: Boonrueng Pawana , Wasana Peththa Wadu Dasuni , Hasriadi  , Vajragupta Opa , Rojsitthisak Pornchai , Towiwat Pasarapa
Published: October 2022

Background

Curcumin and piperine are major bioactive compounds of Curcuma longa and Piper nigrum, widely consumed as spices and flock medicine. The combinational use of these plants is a common practice in Southeast Asia. Synergism between curcumin and piperine has been found in several animal models but not in periodontal disease and diabetes, and the antinociceptive interaction is still unknown. Hence, the present study aimed to assess the interaction between curcumin and piperine in pain and its potential CNS side effect profile.

Methods

Formalin test and in vitro LPS-stimulated RAW 264.7 macrophage cells were used to assess the synergistic interaction of curcumin and piperine in a mouse model of inflammatory pain. Tail-flick and cold plate tests were applied to determine the antinociceptive synergism between piperine and curcumin. The interaction was determined by applying isobolographic analysis. The potential CNS-side effects of the curcumin and piperine combination were also assessed using LABORAS automated home-cage behavioral analysis.

Results

Curcumin alone dose-dependently improved pain-like behaviors in the formalin, tail-flick, and cold plate tests with the ED50 of 71.4, 34.4, and 31.9 mg/kg, respectively. Additionally, piperine exhibited efficacy in the formalin, tail-flick, and cold plate tests with the ED50 of 18.4, 8.1, and 28.1 mg/kg, respectively. The combination of curcumin and piperine (1:1 ED50 ratio) produced synergistic interaction in the formalin, tail-flick, and cold plate tests as assessed significantly lower experimental ED50 values (5.9, 5.2, and 5.5 mg/kg) compared to theoretical ED50 values (44.9, 21.3, and 30.0 mg/kg), isobologram analysis, and interaction index values of 0.13, 0.24 and 0.18, respectively. The synergistic interaction of curcumin and piperine was further confirmed by the efficacy of the combination in LPS-stimulated RAW 264.7 macrophage cells. Curcumin and piperine interacted synergistically, reducing proinflammatory mediators. The combination also demonstrated better compatibility profiles with neuronal cells. Furthermore, the curcumin-piperine combination had no effects on mouse spontaneous locomotor behaviors in LABORAS automated home cage monitoring.

Conclusion

Overall, the present study demonstrates strong antinociceptive synergism between curcumin and piperine in mouse models with no potential CNS side effects, suggesting its possible use in clinical trials.