bluuebunny/crossref_metadata_2025 huggingface dataset:
Paradoxical downregulation of LPAR3 exerts tumor-promoting activity through autophagy induction in Ras-transformed cells
Authors: Hwang Sung-Hee , Kim Hye-Gyo , Lee Michael
Published: September 2022

Background

Lysophosphatidic acid receptor 3 (LPAR3) is coupled to Gαi/oand Gα11/qsignaling. Previously, we reported thatLPAR3is highly methylated in carcinogen-induced transformed cells. Here, we demonstrate that LPAR3 exhibits malignant transforming activities, despite being downregulated in transformed cells.

Methods

The LPAR3 knockout (KO) in NIH 3 T3 and Bhas 42 cells was established using the CRISPR/Cas9 system. Both RT-PCR and DNA sequencing were performed to confirm the KO of LPAR3. The cellular effects of LPAR3 KO were further examined by WST-1 assay, immunoblotting analysis, transwell migration assay, colony formation assay, wound scratch assday, in vitro cell transformation assay, and autophagy assay.

Results

In v-H-ras-transformed cells (Ras-NIH 3 T3) with LPAR3 downregulation, ectopic expression of LPAR3 significantly enhanced the migration. In particular, LPAR3 knockout (KO) in Bhas 42 (v-Ha-ras transfected Balb/c 3 T3) and NIH 3 T3 cells caused a decrease in cell survival, transformed foci, and colony formation. LPAR3 KO led to the robust accumulation of LC3-II and autophagosomes and inhibition of autophagic flux by disrupting autophagosome fusion with lysosome. Conversely, autolysosome maturation proceeded normally in Ras-NIH 3 T3 cells upon LPAR3 downregulation. Basal phosphorylation of MEK and ERK markedly increased in Ras-NIH 3 T3 cells, whereas being significantly lower in LPAR3 KO cells, suggesting that increased MEK signaling is involved in autophagosome–lysosome fusion in Ras-NIH 3 T3 cells.

Conclusions

Paradoxical downregulation of LPAR3 exerts cooperative tumor-promoting activity with MEK activation through autophagy induction in Ras-transformed cells. Our findings have implications for the development of cancer chemotherapeutic approaches.
Machine learning-based improvement of MDS-CBC score brings platelets into the limelight to optimize smear review in the hematology laboratory
Authors: Zhu Jaja , Lemaire Pierre , Mathis Stéphanie , Ronez Emily , Clauser Sylvain , Jondeau Katayoun , Fenaux Pierre , Adès Lionel , Bardet Valérie
Published: September 2022

Background

Myelodysplastic syndromes (MDS) are clonal hematopoietic diseases of the elderly characterized by chronic cytopenias, ineffective and dysplastic haematopoiesis, recurrent genetic abnormalities and increased risk of progression to acute myeloid leukemia. A challenge of routine laboratory Complete Blood Counts (CBC) is to correctly identify MDS patients while simultaneously avoiding excess smear reviews. To optimize smear review, the latest generations of hematology analyzers provide new cell population data (CPD) parameters with an increased ability to screen MDS, among which the previously described MDS-CBC Score, based on Absolute Neutrophil Count (ANC), structural neutrophil dispersion (Ne-WX) and mean corpuscular volume (MCV). Ne-WX is increased in the presence of hypogranulated/degranulated neutrophils, a hallmark of dysplasia in the context of MDS or chronic myelomonocytic leukemia. Ne-WX and MCV are CPD derived from leukocytes and red blood cells, therefore the MDS-CBC score does not include any platelet-derived CPD. We asked whether this score could be improved by adding the immature platelet fraction (IPF), a CPD used as a surrogate marker of dysplastic thrombopoiesis.

Methods

Here, we studied a cohort of more than 500 individuals with cytopenias, including 168 MDS patients. In a first step, we used Breiman’s random forests algorithm, a machine-learning approach, to identify the most relevant parameters for MDS prediction. We then designed Classification And Regression Trees (CART) to evaluate, using resampling, the effect of model tuning parameters on performance and choose the “optimal” model across these parameters.

Results

Using random forests algorithm, we identified Ne-WX and IPF as the strongest discriminatory predictors, explaining 37 and 33% of diagnoses respectively. To obtain “simplified” trees, which could be easily implemented into laboratory middlewares, we designed CART combining MDS-CBC score and IPF. Optimal results were obtained using a MDS-CBC score threshold equal to 0.23, and an IPF threshold equal to 3%.

Conclusions

We propose an extended MDS-CBC score, including CPD from the three myeloid lineages, to improve MDS diagnosis on routine laboratory CBCs and optimize smear reviews.
Is laterality in breast Cancer still worth studying? Local experience in Bahrain
Authors: Al Saad Suhair , Al Shenawi Hamdi , Almarabheh Amer , Al Shenawi Noor , Mohamed Abdulla Ismaeel , Yaghan Rami
Published: September 2022

Background

Laterality in breast cancer means an increased frequency of left-sided breast cancers compared to right-sided breast cancers ranging between 1.05 and 1.26. It was first described in 1935 by Fellenberg, Sweden. The explanation of this phenomenon is not clear, but the association with other factors was found. This study aimed to explore the laterality of breast cancer in Bahrain as a model for Arabian countries. The association of laterality with the clinicopathological characteristics of the tumor was also analyzed to explore any applied clinical value.

Methods

This is a cross-sectional, retrospective review of a particular ethnic population to study laterality of breast cancer versus a number of clinicopathological factors, as well as prognosis. The study analyzed 228 breast cancer patients treated in Arabian Gulf University facilities in Bahrain between 1999 and 2020. Three bilateral breast cancer and two malignant phyllodes patients were excluded.

The following variables were analyzed: laterality ratio (Lt/Rt) and the association between laterality and clinicopathological characteristics (age at diagnosis, family history of malignancy, size of the tumor, tumor grade, histological type, hormonal receptors and HER2, axillary lymph node status, tumor stage, five-year survival rate, nulliparity, and multifocality).

Results

The laterality ratio (Lt/Rt) was 1.06 and was 0.97 for patients below 50 years of age, and 1.19 for patients 50 years of age and above.

Analysis of our data showed a statistically significant association between laterality and tumor stage (p. value =0.025) at presentation, and laterality and family history of malignancy (p. value =0.052).

Right-sided breast cancer was associated with a higher positive family history of malignancy and an increased ratio of locally advanced and metastatic disease, and a reduced 5-year survival in relation to size and stage. Left-sided breast cancer was associated with higher early tumor stage.

Conclusion

This is the first study exploring the issue of breast cancer laterality in a defined Arabian population. The laterality ratio in this study was 1.06, which is consistent with the globally published range (1.05 to 1.26) and is increasing with increasing age.

The association between breast cancer laterality, and the hormonal and HER2 is still not widely addressed in the available literature, although other clinicopathological characteristics were extensively analyzed.
The effects of topical cycloplegics in acute acquired comitant esotropia induced by excessive digital device usage
Authors: Hayashi Rijo , Hayashi Shimmin , Machida Shigeki
Published: September 2022

Background

Acute acquired comitant esotropia induced by excessive digital device usage, especially smartphones (SAACE), has been increasing over the past few years. One suggested mechanism is convergence spasm induced by excessive near work, with refraining from digital device use considered to be an effective method for decreasing the degree of esodeviation. However, if symptoms persist and are untreated over time, recovery becomes more difficult. The present study evaluated the effects of topical cycloplegics on persistent SAACE untreated for over 1 year.

Methods

Patients with sustained SAACE that was untreated for over 1 year were evaluated. Digital device usage was discouraged and a topical cycloplegic, 0.4% tropicamide, was prescribed at bedtime. After obtaining informed consent, the 14 out of 23 enrolled patients who agreed to eye drop administration were defined as the study group, with the others serving as the controls. After a 3-month follow-up, patients who elected to undergo surgery were analyzed as the surgery group. Changes in esotropia angles, stereoacuity and diplopia complaints were evaluated after a 3-month follow-up.

Results

Esotropia angles decreased and stereoacuity improved after a 3-month treatment in the study group (P < 0.01). Diplopia disappeared in 13 patients (92.9%, totally disappeared or disappeared when using glasses with built-in prisms). Among 11 patients with untreated esotropia ranging from 1–3 years, decreases in esotropia angles were correlated to untreated esotropia duration (near: R = -0.6; distance: R = 0.7; both P < 0.05). Esotropia angles in the control group exhibited a tendency to increase while stereoacuity tended to deteriorate after the 3-month follow-up. As diplopia did not disappear in any patients, 7 elected to undergo surgery and were enrolled as the surgery group. While esotropia angles decreased in the study group, they were lower than the surgery group (P < 0.01), but higher than the control group (P < 0.01). Stereoacuity was worse in the control versus the study and surgery groups (both P < 0.05).

Conclusion

Results suggest short-acting topical cycloplegics are effective in SAACE patients with long untreated periods. Decreases in esotropia angles were negatively correlated to untreated esotropia duration, which suggests the necessity of early treatment.
Latent classes of posttraumatic stress disorder among survivors of the Bam Earthquake after 17 years
Authors: Abolhadi Elham , Divsalar Parisa , Mosleh-Shirazi Mohammad Amin , Dehesh Tania
Published: September 2022

Background

The purpose of this study was to identify latent classes of the severity of post-traumatic stress disorder (PTSD) among the survivors of the earthquake in Bam, south-eastern Iran, 17 years after the disaster. The most influential predictor variables of PTSD classes were also investigated.

Methods

Eight hundred survivors of the Bam earthquake who were at least four years old in that disaster were selected by multistage sampling. The PTSD Checklist-Civilian Version was used. Latent class analysis was performed to identify subgroups of people with different PTSD symptom profiles. Latent class regression analysis was used to explore the influence of demographic and traumatic variables on each class membership.

Results

We found three latent classes of PTSD, with the following profiles emerging: Low Symptom (56.6% of the participants), Moderate Symptom (23.5%), and Severe Symptom (19.9%). Old age [OR = 2.20, 95% CI = (1.46, 3.32)], physical injury [OR = 1.95, 95% CI = (1.24, 3.06)], being trapped under the rubble [OR = 1.81, 95% CI = (1.15, 2.86)], and death of a family member [OR = 1.86, 95% CI = (1.12, 3.09)] were positive risk factors for PTSD and increased the chance of being in classes having more severe symptoms. Having a high educational level was a negative risk factor [OR = 0.86, 95% CI = (0.67, 1.11)].

Conclusions

The severity of PTSD 17 years after the earthquake shows that natural disasters such as earthquakes have long-term consequences, and earthquake survivors must have psychological support and long term health care.

After any catastrophic earthquake, governments should establish psychology and psychotherapy centers for earthquake victims, and these centers should support earthquake victims for a sufficiently long time.
Feeding, caregiving practices, and developmental delay among children under five in lowland Nepal: a community-based cross-sectional survey
Authors: Dulal Sophiya , Prost Audrey , Karki Surendra , Merom Dafna , Shrestha Bhim Prasad , Bhandari Bishnu , Manandhar Dharma S. , Osrin David , Costello Anthony , Saville Naomi M.
Published: September 2022

Background

Nurturing care, including adequate nutrition, responsive caregiving and early learning, is critical to early childhood development. In Nepal, national surveys highlight inequity in feeding and caregiving practices for young children. Our objective was to describe infant and young child feeding (IYCF) and cognitive and socio-emotional caregiving practices among caregivers of children under five in Dhanusha district, Nepal, and to explore socio-demographic and economic factors associated with these practices.

Methods

We did a cross-sectional analysis of a subset of data from the MIRA Dhanusha cluster randomised controlled trial, including mother-child dyads (N = 1360), sampled when children were median age 46 days and a follow-up survey of the same mother-child dyads (N = 1352) when children were median age 38 months. We used World Health Organization IYCF indicators and questions from the Multiple Indicator Cluster Survey-4 tool to obtain information on IYCF and cognitive and socio-emotional caregiving practices. Using multivariable logistic regression models, potential explanatory household, parental and child-level variables were tested to determine their independent associations with IYCF and caregiving indicators.

Results

The prevalence of feeding indicators varied. IYCF indicators, including ever breastfed (99%), exclusive breastfeeding (24-hour recall) (89%), and vegetable/fruit consumption (69%) were common. Problem areas were early initiation of breastfeeding (16%), colostrum feeding (67%), no pre-lacteal feeding (53%), timely introduction of complementary feeding (56%), minimum dietary diversity (49%) and animal-source food consumption (23%). Amongst caregiving indicators, access to 3+ children’s books (7%), early stimulation and responsive caregiving (11%), and participation in early childhood education (27%) were of particular concern, while 64% had access to 2+ toys and 71% received adequate care. According to the Early Child Development Index score, only 38% of children were developmentally on track. Younger children from poor households, whose mothers were young, had not received antenatal visits and delivered at home were at higher risk of poor IYCF and caregiving practices.

Conclusions

Suboptimal caregiving practices, inappropriate early breastfeeding practices, delayed introduction of complementary foods, inadequate dietary diversity and low animal-source food consumption are challenges in lowland Nepal. We call for urgent integrated nutrition and caregiving interventions, especially as interventions for child development are lacking in Nepal.
A qualitative exploration of Ugandan mental health care workers’ perspectives and experiences on sexual and reproductive health of people living with mental illness in Uganda
Authors: Tumwakire Emily , Arnd Hofmeister , Gavamukulya Yahaya
Published: September 2022

Background

People with Mental Illness experience vast sexual and reproductive health challenges due to the affected mental health. Globally, prevalence of mental illness is on the rise with subsequent increase in the number of people with sexual and reproductive challenges warranting urgent public health intervention. However, information on the perceptions and experiences of mental health workers, the key health care providers for this population is generally lacking yet it’s essential for formulation of appropriate policies and public health interventions.

Aim

To explore Ugandan mental health care worker’s perspectives and experiences on the sexual and reproductive health of people living with mental illness in Uganda in order to generate recommendations to the ministry of health on how it can be improved.

Materials and methods

Qualitative study design was employed with utilization of phone call semi-structured in-depth interviews to collect data from 14 mental health workers from Uganda’s National mental referral hospital, Butabika. Purposive sampling and convenience recruitment was done and the collected data was analyzed using Thematic content analysis.

Results

Four themes were generated which included people with Mental illness having normal sexual needs, mental illness effect on sexuality and relationships, practices for safeguarding sexuality of people with mental illness and the barriers encountered in the provision of sexual and reproductive health services at a mental hospital.

Conclusion

People with mental illness experience a multitude of sexual and reproductive health challenges that need public health interventions. However, the integration of sexual and reproductive health services in a mental hospital are not yet successful making people with mental illness to remain with unaddressed health challenges. Policies should therefore be developed and implemented to ensure successful integration of sexual and reproductive health at all mental health service care provision points.
The feasibility of collecting the physiotherapy outcomes airway clearance, physical activity and fitness for the Australian Cystic Fibrosis Data Registry
Authors: Potter Angela , Singh Ben , Scutter Emily , Maher Carol
Published: September 2022

Background

Physiotherapy-related data, such as airway clearance techniques (ACTS), physical activity and aerobic fitness are not consistently included in international cystic fibrosis (CF) data registries. This study aimed to pilot the collection of ACTS, physical activity and fitness in a hospital CF clinic, as a step towards informing future national implementation.

Methods

This study was undertaken in a CF clinic within a major tertiary hospital. Patients and families were invited to participate. Participants completed self-report questionnaires on ACT use and those aged ≥ 10 years completed a physical activity questionnaire (Core Indicators and Measures of Youth Health Survey) and aerobic fitness test (the A-STEP test). Participants also completed a survey to explore the tolerance and acceptability of the fitness test, and the perceived accuracy of the self-reported data collection.

Results

Forty patients agreed to participate in the study (mean age = 9.8, SD = 4.1 years old; 52.5% female). All patients and/or families that were approached agreed to participate and completion rate for the ACTs and physical activity surveys was 98% and 100% (respectively). Completion rate for the fitness test was 55%, due to time constraints. Most participants agreed (≥ 90%) they could accurately provide ACT and physical activity data, and the assessments were tolerable and acceptable.

Conclusions

Patients with CF and their families are able to and can acceptably provide physiotherapy-related data, and collecting self-report ACTs and physical activity data is highly feasibly during routine CF clinic visits. However, aerobic fitness testing using the A-STEP test may be less feasible in clinic environments, due to time constraints.
The clinical outcomes and complications of combined fixation with cannulated screws and the modified Pyrford technique for the treatment of transverse patellar fractures: a case series study
Authors: Li Yihan , Tian Qingxian , Leng Kunpeng , Guo Meng
Published: September 2022

Background

Transverse patellar fractures can be fixed using various techniques. The purpose of the current study was to assess the clinical outcomes and complication rate of a combined fixation technique using cannulated screws and the modified Pyrford technique with nonabsorbable polyester sutures.

Methods and patients

Between January 2015 and February 2021, 26 transverse patellar fractures were fixed with this combined technique. Preoperative data were collected from patients with transverse patellar fractures who were followed up for at least 12 months. At each follow-up visit, plain radiographs were taken. At the 12-month postoperative follow-up, range of motion of the affected knee joint and clinical outcomes, as evaluated by the Bostman scoring system, were recorded.

Results

The average Bostman score at the 12-month postoperative follow-up was 28.3 ± 1.5. Furthermore, the average extension and flexion of the knee joint were 1.2 ± 2.1 and 125.6 ± 6.7 degrees, respectively. One patient experienced delayed bone union and one experienced superficial wound infection. There were no other postoperative complications. One patient required removal of the device for social-psychological reasons.

Conclusions

The combined fixation technique with cannulated screws and the modified Pyrford technique with suture materials produced excellent clinical outcomes and a low rate of complications in the treatment of transverse patellar fractures.
Medical decision-making in hospices from the viewpoint of physicians: results from two qualitative studies
Authors: Walker Andreas , Breitsameter Christof
Published: September 2022

Background

Physicians who practice in a hospice are responsible for working with patients and nursing staff to develop a medication plan, monitor symptoms and pain, and adjust medication if necessary. In inpatient hospices in Germany, physicians are part of a multi-professional approach, but not part of the hospice team itself. However, there is no, or hardly any, literature on medical practice in a hospice setting. Therefore, we wanted to know how physicians reflect upon their role in hospice within a multi-professional setting, how they communicate with patients, relatives, nursing staff and other physicians, and what the limitations of these communication processes are.

Methods

By means of two qualitative studies we explored how physicians classify their activities as part of the hospice organization. The study design followed Grounded Theory procedures.

Results

The physicians named an appropriate interpretation of the patient's wishes as the challenge of everyday practice which can lead to differences of perspective with those involved: with nursing staff, who would prefer an alternative form of medication, with relatives, who do not accept that the patient refuses nutrition, with other physicians, who have a different opinion about appropriate treatment. For physicians, this is all the more challenging as communication with the patient becomes increasingly uncertain due to the patient’s illness. Again and again, medical measures have to be negotiated on several levels.

Conclusion

Multi-professional organizations that have to deal with differences in perspective handle them by clearly distinguishing areas of responsibility, an aspect that physicians also claim for themselves. For physicians the question arises repeatedly whether they have correctly interpreted the wishes of the patient. They must continuously reassure themselves of the patient's wishes and this presents them with communication challenges not only with the patient, but also with the nursing staff and relatives and, more recently, with their colleagues.
The role of the ICU liaison nurse services on anxiety in family caregivers of patients after ICU discharge during COVID-19 pandemic: a randomized controlled trial
Authors: Mottaghi Khadijeh , Hasanvand Shirin , Goudarzi Fateme , Heidarizadeh Khadijeh , Ebrahimzadeh Farzad
Published: September 2022

Background

With the onset of the COVID-19 pandemic and the need to maintain social distancing and changes in wards' structure, families no longer access the routine support they received during the hospitalization of their patients in the ICU. This study aimed to determine the effects of ICU liaison nurse services on the anxiety in patients’ family caregivers after ICU discharge during the COVID-19 pandemic.

Methods

This randomized controlled trial was performed in western Iran from February 2020, to March 2021. Sixty subjects were selected from the family caregivers of the patients transferred from the ICU and were randomly assigned to the control (n = 30) and the intervention groups (n = 30). The control group received routine transfer care. In the intervention group, liaison nurse services were offered in 4 dimensions: patient support, family support, training, support of the ward’s staff, and the evaluation of the destination ward. The participants’ anxiety was measured using the Spielberger State Anxiety Inventory immediately after the patient transfer and 6 h after admission to the general ward. Data analyzed with SPSS V16, descriptive and inferential statistics, including Chi-square test, Mann–Whitney test, Wilcoxon test, and Generalized Linear Model with cumulative logit link function. Results were reported at a 0.05 significance level.

Results

A statistically significant difference was observed in baseline anxiety levels (P = 0.035) and age group (P < 0.001) between the intervention and control groups. After moderating baseline anxiety levels, the age group, and marital status, the impact of the intervention was significant (X2 = 10.273, df = 1, P < 0.001), meaning that the intervention could reduce the relative chances of developing higher levels of anxiety by 92.1% (OR: 0.08, 95%CI: 0.017–0.373, P < 0.001).

Conclusions

This study confirmed the positive impact of nursing services on reducing anxiety in family caregivers during the COVID-19 pandemic. It is recommended to use these services, especially during the COVID-19 condition, to facilitate the patient transfer, support the patient's family, and reduce the health care gap between the ICU and the ward.
A novel strategy for developing vaccine candidate against Jaagsiekte sheep retrovirus from the envelope and gag proteins: an in-silico approach
Authors: Mahmoud Nuha Amin , Elshafei Abdelmajeed M. , Almofti Yassir A.
Published: September 2022

Background

Sheep pulmonary adenocarcinoma (OPA) is a contagious lung cancer of sheep caused by the Jaagsiekte retrovirus (JSRV). OPA typically has a serious economic impact worldwide. A vaccine has yet to be developed, even though the disease has been globally spread, along with its complications. This study aimed to construct an effective multi-epitopes vaccine against JSRV eliciting B and T lymphocytes using immunoinformatics tools.

Results

The designed vaccine was composed of 499 amino acids. Before the vaccine was computationally validated, all critical parameters were taken into consideration; including antigenicity, allergenicity, toxicity, and stability. The physiochemical properties of the vaccine displayed an isoelectric point of 9.88. According to the Instability Index (II), the vaccine was stable at 28.28. The vaccine scored 56.51 on the aliphatic index and -0.731 on the GRAVY, indicating that the vaccine was hydrophilic. The RaptorX server was used to predict the vaccine's tertiary structure, the GalaxyWEB server refined the structure, and the Ramachandran plot and the ProSA-web server validated the vaccine's tertiary structure. Protein-sol and the SOLPro servers showed the solubility of the vaccine. Moreover, the high mobile regions in the vaccine’s structure were reduced and the vaccine’s stability was improved by disulfide engineering. Also, the vaccine construct was docked with an ovine MHC-1 allele and showed efficient binding energy. Immune simulation remarkably showed high levels of immunoglobulins, T lymphocytes, and INF-γ secretions. The molecular dynamic simulation provided the stability of the constructed vaccine. Finally, the vaccine was back-transcribed into a DNA sequence and cloned into a pET-30a ( +) vector to affirm the potency of translation and microbial expression.

Conclusion

A novel multi-epitopes vaccine construct against JSRV, was formed from B and T lymphocytes epitopes, and was produced with potential protection. This study might help in controlling and eradicating OPA.
Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations
Authors: Anwar Mohammad Yaser , Baldassari Antoine R. , Polikowsky Hannah G. , Sitlani Colleen M. , Highland Heather M. , Chami Nathalie , Chen Hung-Hsin , Graff Mariaelisa , Howard Annie Green , Jung Su Yon , Petty Lauren E. , Wang Zhe , Zhu Wanying , Buyske Steven , Cheng Iona , Kaplan Robert , Kooperberg Charles , Loos Ruth J. F. , Peters Ulrike , McCormick Joseph B. , Fisher-Hoch Susan P. , Avery Christy L. , Taylor Kira C. , Below Jennifer E. , North Kari E.
Published: September 2022

Background

Concurrent variation in adiposity and inflammation suggests potential shared functional pathways and pleiotropic disease underpinning. Yet, exploration of pleiotropy in the context of adiposity-inflammation has been scarce, and none has included self-identified Hispanic/Latino populations. Given the high level of ancestral diversity in Hispanic American population, genetic studies may reveal variants that are infrequent/monomorphic in more homogeneous populations.

Methods

Using multi-trait Adaptive Sum of Powered Score (aSPU) method, we examined individual and shared genetic effects underlying inflammatory (CRP) and adiposity-related traits (Body Mass Index [BMI]), and central adiposity (Waist to Hip Ratio [WHR]) in HLA participating in the Population Architecture Using Genomics and Epidemiology (PAGE) cohort (N = 35,871) with replication of effects in the Cameron County Hispanic Cohort (CCHC) which consists of Mexican American individuals.

Results

Of the > 16 million SNPs tested, variants representing 7 independent loci were found to illustrate significant association with multiple traits. Two out of 7 variants were replicated at statistically significant level in multi-trait analyses in CCHC. The lead variant on APOE (rs439401) and rs11208712 were found to harbor multi-trait associations with adiposity and inflammation.

Conclusions

Results from this study demonstrate the importance of considering pleiotropy for improving our understanding of the etiology of the various metabolic pathways that regulate cardiovascular disease development.
Prognostic value of soluble ST2, high-sensitivity cardiac troponin, and NT-proBNP in type 2 diabetes: a 15-year retrospective study
Authors: Sabbatinelli Jacopo , Giuliani Angelica , Bonfigli Anna Rita , Ramini Deborah , Matacchione Giulia , Campolucci Carla , Ceka Artan , Tortato Elena , Rippo Maria Rita , Procopio Antonio Domenico , Moretti Marco , Olivieri Fabiola
Published: September 2022

Background

Patients with type 2 diabetes (T2DM) present an increased risk of cardiovascular (CV) disease and excess CV-related mortality. Beyond the established role of brain natriuretic peptide (BNP) and cardiac troponins (cTn), other non-cardiac-specific biomarkers are emerging as predictors of CV outcomes in T2DM.

Methods

Serum levels of soluble suppression of tumorigenesis 2 (sST2), high-sensitivity (hs)-cTnI, and N-terminal (NT)-proBNP were assessed in 568 patients with T2DM and 115 healthy controls (CTR). Their association with all-cause mortality and the development of diabetic complications was tested in T2DM patients over a median follow-up of 16.8 years using Cox models and logistic regressions.

Results

sST2 followed an increasing trend from CTR to uncomplicated T2DM patients (T2DM-NC) to patients with at least one complication (T2DM-C), while hs-cTnI was significantly higher in T2DM-C compared to CTR but not to T2DM-NC. A graded association was found between sST2 (HR 2.76 [95% CI 1.20–6.33] for ≥ 32.0 ng/mL and 2.00 [1.02–3.94] for 16.5–32.0 ng/mL compared to < 16.5 ng/mL, C-statistic = 0.729), NT-proBNP (HR 2.04 [1.90–4.55] for ≥ 337 ng/L and 1.48 [1.05–2.10] for 89–337 ng/L compared to < 89 ng/L, C-statistic = 0.741), and 15-year mortality in T2DM, whereas increased mortality was observed in patients with hs-cTnI ≥ 7.8 ng/L (HR 1.63 [1.01–2.62]). A ‘cardiac score’ based on the combination of sST2, hs-cTnI, and NT-proBNP was significantly associated with all-cause mortality (HR 1.35 [1.19–1.53], C-statistic = 0.739) and development of CV events.

Conclusions

sST2, hs-cTnI, and NT-proBNP are associated with 15-year mortality and onset of CV events in T2DM. The long-term prognostic value of sST2 and its ability to track variables related to insulin resistance and associated metabolic disorders support its implementation into routine clinical practice.
Transcriptome analysis of the production enhancement mechanism of antimicrobial lipopeptides of Streptomyces bikiniensis HD-087 by co-culture with Magnaporthe oryzae Guy11
Authors: Liu Wei , Wang Jiawen , Zhang Huaqian , Qi Xiaohua , Du Chunmei
Published: September 2022

The lipopeptides produced by Streptomyces bikiniensis have a significant inhibitory effect on Magnaporthe oryzae, but the low yield limits its application. In this study, the anti-M. oryzae activity of the broth of S. bikiniensis HD-087 co-cultured with M. oryzae Guy11 mycelium has risen by 41.22% compared with pure culture, and under induction conditions of adding Guy11-inducer (cell-free supernatant of M. oryzae Guy11), the activity of strain HD-087 improved 61.76%. The result proved that the enhancement effect of Guy11 on the antimicrobial activity of HD-087 was mainly related to metabolites but mycelium cells. Under optimum induction conditions, NRPS gene expression levels of HD-087 were significantly increased by induction with Guy11-inducer, the biomass of HD-087 had no significant change, but crude extract of lipopeptide (CEL) production was 107.4% higher than pure culture, and TLC result under acid hydrolysis showed that the induced culture has one component more than pure culture. To clarify the regulation mechanism of improving lipopeptide production of HD-087 with Guy11-inducer, transcriptomic analysis was performed using RNAseq to compare the induced culture and pure culture. In the induced culture, 943 genes were up-regulated, while 590 genes were down-regulated in DEGs (differentially expressed genes). KEGG results showed that the expression of genes related to amino acid synthesis, fatty acid metabolism, TCA cycle and pyruvate metabolism pathway were significantly increased. The increased expression of genes related to these metabolic pathways provided sufficient precursors for lipopeptide synthesis. Accordingly, key enzyme genes responsible for the synthesis of lipopeptides Srf and NRPS was significantly increased. Quorum sensing related genes OppA and MppA were significantly up-regulated, and then ComP was activated and promoted lipopeptide synthesis. These results provided a scientific basis for using M. oryzae to induce the increase of the production of Streptomyces lipopeptides, and also laid a foundation for further exploring the co-culture mechanisms among different genera.
Deciphering the pathway-specific regulatory network for production of ten-membered enediyne Tiancimycins in Streptomyces sp. CB03234-S
Authors: Zhu Manxiang , Zhang Fan , Gan Ting , Lin Jing , Duan Yanwen , Zhu Xiangcheng
Published: September 2022

Background

The anthraquinone-fused 10-membered enediynes (AFEs), represented by tiancimycins (TNMs), possess a unique structural feature and promising potentials as payloads of antitumor antibody–drug conjugates. Despite many efforts, the insufficient yields remain a practical challenge for development of AFEs. Recent studies have suggested a unified basic biosynthetic route for AFEs, those core genes involved in the formation of essential common AFE intermediates, together with multiple regulatory genes, are highly conserved among the reported biosynthetic gene clusters (BGCs) of AFEs. The extreme cytotoxicities of AFEs have compelled hosts to evolve strict regulations to control their productions, but the exact roles of related regulatory genes are still uncertain.

Results

In this study, the genetic validations of five putative regulatory genes present in the BGC of TNMs revealed that only three (tnmR1, tnmR3 and tnmR7) of them were involved in the regulation of TNMs biosynthesis. The bioinformatic analysis also revealed that they represented three major but distinct groups of regulatory genes conserved in all BGCs of AFEs. Further transcriptional analyses suggested that TnmR7 could promote the expressions of core enzymes TnmD/G and TnmN/O/P, while TnmR3 may act as a sensor kinase to work with TnmR1 and form a higher class unconventional orphan two-component regulatory system, which dynamically represses the expressions of TnmR7, core enzymes TnmD/G/J/K1/K2 and auxiliary proteins TnmT2/S2/T1/S1. Therefore, the biosynthesis of TNMs was stringently restricted by this cascade regulatory network at early stage to ensure the normal cell growth, and then partially released at the stationary phase for product accumulation.

Conclusion

The pathway-specific cascade regulatory network consisting with TnmR3/R1 and TnmR7 was deciphered to orchestrate the production of TNMs. And it could be speculated as a common regulatory mechanism for productions of AFEs, which shall provide us new insights in future titer improvement of AFEs and potential dynamic regulatory applications in synthetic biology.
Medicinal plants used in traditional treatment of malaria in Ethiopia: a review of ethnomedicine, anti-malarial and toxicity studies
Authors: Nigussie Gashaw , Wale Minychel
Published: September 2022

Background

Malaria is extremely common in Ethiopia, and it is one of the country's most serious public health and economic problems. Traditional medicines have long been utilized in Ethiopia by people of various ethnic groups. As a result, the goal of this study is to record the use of Ethiopian medicinal herbs that have been used to treat malaria. Also, a critical review of the literature on the therapeutic properties of these and other Ethiopian medicinal plants that have been tested againstPlasmodiumspp.parasites was conducted with the goal of highlighting neglected studies and fostering further research in this area.

Methods

A comprehensive literature search was performed in Scopus, Web of Science Core Collection, PubMed, Science Direct, Google Scholar, and Scientific Electronic Library Online (SciELO) from August 2021 to October 2021. The study databases included original articles published in peer reviewed journals covering anti-malarial plants, dated until October 2021.

Results

The review looked at 51 plant species (28 families) that have been used to treat malaria in Ethiopia. The most often used ethnobotanical plant species for the treatment of malaria wereAllium sativum,Croton macrostachyus,Carica papaya, andLepidium sativum. Leaves were used more frequently as a therapeutic preparation than other parts. Plant extracts were found to have very good, good, and moderate anti-malarial activity in mice with rodentPlasmodiumspecies. The most active species wereAjuga remotaandCapsicum frufescens, which suppressed parasitaemia by 77.34% and 72.65%, respectively, at an oral dose of 100 mg/kg and an LD50of above 2000 mg/kg. The compound Aloinoside reported fromAloe macrocarpaleave latex was the most potent; it suppressed parasitaemia by 100% at 400 mg/kg oral dose ofPlasmodium bergheiinfected mice, and its LD50was above 2000 mg/kg. Toxicity was shown to be safe in 84% of the plant extracts.

Conclusion

In Ethiopia, medicinal plants have a significant part in reducing the severity of malaria due to their widespread use. As a result, more studies are needed to identify and develop effective novel drugs that could be employed in broader malaria eradication efforts.
Tackling health inequalities in a public health organization: the case of the Barcelona Public Health Agency
Authors: Pérez Gloria , Pasarín M. Isabel , Puig-Barrachina Vanessa , Pérez Katherine , Rodríguez-Sanz Maica , Artazcoz Lucia , Borrell Carme
Published: September 2022

Background

Municipalities are important actors in the implementation of policies to tackle health inequalities, which requires political will, the availability of financial support, and technical and human resources. With the aim of aligning with local government political priorities, in 2017 the Barcelona Public Health Agency (Agència de Salut Pública de Barcelona, henceforth ASPB), which is responsible for the public health functions of the city, launched a strategy to improve the approach to tackling health inequalities in all its services. The objectives of this study were to show how social health inequalities were addressed in the ASPB from 2017 to 19 and to describe which actions were proposed after a participatory process aiming to create a plan to systematically incorporate health inequalities in ASPB actions.

Methods

The ASPB has 304 workers, 8 directors and 20 services or departments. Participatory methodologies were carried out: 1) semi-structured interviews with department heads (N = 12, 60%); 2) world cafe workshops open to a group of workers (N = 63, 37%); 3) aQuick and Colorfulvoting session open to a group of workers (N = 108, 63%); and 4) Hanlon matrix with 19 actions to be prioritized (N = 12 services, 60%).

Results

Semi-structured interviews and world cafe workshops provided 40 potential actions. After a step by step process of participatory prioritization, seven lines of action emerged: 1) to make progress in collaborative networking; 2) to promote policy evaluation; 3) to increase the ability of the ASPB to evaluate policies to reduce health inequalities; 4) to incorporate the axes of inequalities in all ASPB products; 5) to improve information on vulnerable groups; 6) to incorporate the gender perspective; and 7) to participate in an internal training plan to address health inequalities.

Conclusions

The participation of ASPB public health professionals and staff allowed the organization to design a shared plan of actions to address health inequalities. This experience could be useful for other municipalities whose political agendas include tackling inequalities in health.
Lipid metabolism patterns and relevant clinical and molecular features of coronary artery disease patients: an integrated bioinformatic analysis
Authors: Liao Yanhui , Dong Zhenzhen , Liao Hanhui , Chen Yang , Hu Longlong , Yu Zuozhong , Xia Yi , Zhao Yuanbin , Fan Kunpeng , Ding Jingwen , Yao Xiongda , Deng Tianhua , Yang Renqiang
Published: September 2022

Background

Hyperlipidaemia is an important factor that induces coronary artery disease (CAD). This study aimed to explore the lipid metabolism patterns and relevant clinical and molecular features of coronary artery disease patients.

Methods

In the current study, datasets were fetched from the Gene Expression Omnibus (GEO) database and nonnegative matrix factorization clustering was used to establish a new CAD classification based on the gene expression profile of lipid metabolism genes. In addition, this study carried out bioinformatics analysis to explore intrinsic biological and clinical characteristics of the subgroups.

Results

Data for a total of 615 samples were extracted from the Gene Expression Omnibus database and were associated with clinical information. Then, this study used nonnegative matrix factorization clustering for RNA sequencing data of 581 lipid metabolism relevant genes, and the 296 patients with CAD were classified into three subgroups (NMF1, NMF2, and NMF3). Subjects in subgroup NMF2 tended to have an increased severity of CAD. The CAD index and age of group NMF1 were similar to those of group NMF3, but their intrinsic biological characteristics exhibited significant differences. In addition, weighted gene coexpression network analysis (WGCNA) was used to determine the most important modules and screen lipid metabolism related genes, followed by further analysis of the DEGs in which the significant genes were identified based on clinical information. The progression of coronary atherosclerosis may be influenced by genes such as PTGDS and DGKE.

Conclusion

Different CAD subgroups have their own intrinsic biological characteristics, indicating that more personalized treatment should be provided to patients in each subgroup, and some lipid metabolism related genes (PDGTS, DGKE and so on) were related significantly with clinical characteristics.
The significance of the social and material environment to place attachment and quality of life: findings from a large population-based health survey
Authors: Friesinger Jan Georg , Haugland Siri Håvås , Vederhus John-Kåre
Published: September 2022

Background

There is an international public health interest in sustainable environments that promote human wellbeing. An individual’s bond to places, understood as place attachment (PA), is an important factor for quality of life (QoL). The material environment, such as access to nature (AtN), access to amenities (AtA), or noise, and the social environment, such as social support or loneliness, has the potential to influence PA. The aim of the present study was to explore the relationship between these factors and QoL.

Methods

The study relied on data from 28,047 adults from 30 municipalities in Southern Norway obtained from the Norwegian Counties Public Health Surveys in 2019. Latent regression analyses were used to examine the relationship between the material and social environmental factors and QoL, mediated by PA.

Results

We found a relationship between social and material environmental factors and PA. Higher AtN and AtA scores were related to an increase in PA, whereas higher perception of noise problems was related to decreased PA scores. When social environment factors were added to the model, they were even stronger predictors of PA and, in turn, QoL through mediated effects. We also found a strong positive association between PA and QoL (unstandardized β = 0.88, 95% CI = 0.87–0.90, p < 0.001). The whole model explained 83% of the variance in PA and 65% of the variance in QoL.

Conclusions

Taken together, the findings suggest the relevance of material and social environmental factors for PA and QoL. Therefore, research on public health and QoL should include place-sensitive variables.
The significance of anatomical variation of the inferior mesenteric artery and its branches for laparoscopic radical resection of colorectal cancer: a review
Authors: Zeng Shun , Wu Wenhao , Zhang Xianbin , Qiu Tong , Gong Peng
Published: September 2022

Currently, high or low ligation of the inferior mesenteric artery (IMA) is a controversial issue in laparoscopic radical surgery for colorectal cancer. High or low ligation of the IMA has both advantages and disadvantages, and the level of ligation during the left colon and/or rectum resection has been a dilemma for surgeons. One important factor influencing the surgeon’s decision to ligate the IMA in a high or low position is the anatomical type of the IMA and its branches. Some studies confirm that the anatomy of the IMA and its branches is critical to the anastomotic blood supply and, therefore, influences the choice of surgical approach (level of ligation of the IMA). However, many vascular variations in the anatomy of the IMA and its branches exist. Herein, we have summarized the anatomical types of the IMA and its branches, finding that the classification proposed by Yada et al. in 1997 is presently accepted by most scholars. Based on Yada’s classification, we further summarized the characteristics of the IMA’s various anatomical types as a guide for high or low ligation in radical colorectal cancer surgery.