bluuebunny/crossref_metadata_2025 huggingface dataset:
HBx facilitates ferroptosis in acute liver failure via EZH2 mediated SLC7A11 suppression
Authors: Liu Guo-Zhen , Xu Xu-Wen , Tao Shu-Hui , Gao Ming-Jian , Hou Zhou-Hua
Published: October 2021

Background

Acute liver failure (ALF) is a syndrome of severe hepatocyte injury with high rate of mortality. Hepatitis B virus (HBV) infection is the major cause of ALF worldwide, however, the underlying mechanism by which HBV infection leads to ALF has not been fully disclosed.

Methods

D-GalN-induced hepatocyte injury model and LPS/D-GalN-induced ALF mice model were used to investigate the effects of HBV X protein (HBx) in vitro and in vivo, respectively. Cell viability and the levels of Glutathione (GSH), malondialdehyde (MDA) and iron were measured using commercial kits. The expression of ferroptosis-related molecules were detected by qRT-PCR and western blotting. Epigenetic modification and protein interaction were detected by chromatin immunoprecipitation (ChIP) assay and co-immunoprecipitation (co-IP), respectively. Mouse liver function was assessed by measuring aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The histological changes in liver tissues were monitored by hematoxylin and eosin (H&E) staining, and SLC7A11 immunoreactivity was assessed by immunohistochemistry (IHC) analysis.

Results

D-GalN triggered ferroptosis in primary hepatocytes. HBx potentiated D-GalN-induced hepatotoxicity and ferroptosis in vitro, and it suppressed SLC7A11 expression through H3K27me3 modification by EZH2. In addition, EZH2 inhibition or SLC7A11 overexpression attenuated the effects of HBx on D-GalN-induced ferroptosis in primary hepatocytes. The ferroptosis inhibitor ferrostatin-1 (Fer-1) protected against ALF and ferroptosis in vivo. By contrast, HBx exacerbates LPS/D-GalN-induced ALF and ferroptosis in HBx transgenic (HBx-Tg) mice.

Conclusion

HBx facilitates ferroptosis in ALF via EZH2/H3K27me3-mediated SLC7A11 suppression.
Primary care-based interventions to address the financial needs of patients experiencing poverty: a scoping review of the literature
Authors: Parry Jane , Vanstone Meredith , Grignon Michel , Dunn James R.
Published: October 2021

Background

It is broadly accepted that poverty is associated with poor health, and the health impact of poverty has been explored in numerous high-income country settings. There is a large and growing body of evidence of the role that primary care practitioners can play in identifying poverty as a health determinant, and in interventions to address it.

Purpose of study

This study maps the published peer-reviewed and grey literature on primary care setting interventions to address poverty in high-income countries in order to identify key concepts and gaps in the research. This scoping review seeks to map the tools in use to identify and address patients’ economic needs; describe the key types of primary care-based interventions; and examine barriers and facilitators to successful implementation.

Methods

Using a scoping review methodology, we searched five databases, the grey literature and the reference lists of relevant studies to identify studies on interventions to address the economic needs-related social determinants of health that occur in primary health care delivery settings, in high-income countries. Findings were synthesized narratively, and examined using thematic analysis, according to iteratively identified themes.

Results

Two hundred and fourteen papers were included in the review and fell into two broad categories of description and evaluation: screening tools, and economic needs-specific interventions. Primary care-based interventions that aim to address patients’ financial needs operate at all levels, from passive sociodemographic data collection upon patient registration, through referral to external services, to direct intervention in addressing patients’ income needs.

Conclusion

Tools and processes to identify and address patients’ economic social needs range from those tailored to individual health practices, or addressing one specific dimension of need, to wide-ranging protocols. Primary care-based interventions to address income needs operate at all levels, from passive sociodemographic data collection, through referral to external services, to direct intervention. Measuring success has proven challenging. The decision to undertake this work requires courage on the part of health care providers because it can be difficult, time-consuming and complex. However, it is often appreciated by patients, even when the scope of action available to health care providers is quite narrow.
Label-free cell based impedance measurements of ZnO nanoparticles—human lung cell interaction: a comparison with MTT, NR, Trypan blue and cloning efficiency assays
Authors: Bozzuto Giuseppina , D’Avenio Giuseppe , Condello Maria , Sennato Simona , Battaglione Ezio , Familiari Giuseppe , Molinari Agnese , Grigioni Mauro
Published: October 2021

Background

There is a huge body of literature data on ZnOnanoparticles (ZnO NPs) toxicity. However, the reported results are seen to be increasingly discrepant, and deep comprehension of the ZnO NPs behaviour in relation to the different experimental conditions is still lacking. A recent literature overview emphasizes the screening of the ZnO NPs toxicity with more than one assay, checking the experimental reproducibility also versus time, which is a key factor for the robustness of the results. In this paper we compared high-throughput real-time measurements through Electric Cell-substrate Impedance-Sensing (ECIS®) with endpoint measurements of multiple independent assays.

Results

ECIS-measurements were compared with traditional cytotoxicity tests such as MTT, Neutral red, Trypan blue, and cloning efficiency assays. ECIS could follow the cell behavior continuously and noninvasively for days, so that certain long-term characteristics of cell proliferation under treatment with ZnO NPs were accessible. This was particularly important in the case of pro-mitogenic activity exerted by low-dose ZnO NPs, an effect not revealed by endpoint independent assays. This result opens new worrisome questions about the potential mitogenic activity exerted by ZnO NPs, or more generally by NPs, on transformed cells. Of importance, impedance curve trends (morphology) allowed to discriminate between different cell death mechanisms (apoptosis vs autophagy) in the absence of specific reagents, as confirmed by cell structural and functional studies by high-resolution microscopy. This could be advantageous in terms of costs and time spent. ZnO NPs-exposed A549 cells showed an unusual pattern of actin and tubulin distribution which might trigger mitotic aberrations leading to genomic instability.

Conclusions

ZnO NPs toxicity can be determined not only by the intrinsic NPs characteristics, but also by the external conditions like the experimental setting, and this could account for discrepant data from different assays. ECIS has the potential to recapitulate the needs required in the evaluation of nanomaterials by contributing to the reliability of cytotoxicity tests. Moreover, it can overcome some false results and discrepancies in the results obtained by endpoint measurements. Finally, we strongly recommend the comparison of cytotoxicity tests (ECIS, MTT, Trypan Blue, Cloning efficiency) with the ultrastructural cell pathology studies.

Graphic Abstract
Photothermal hydrogel platform for prevention of post-surgical tumor recurrence and improving breast reconstruction
Authors: Yang Xi , Gao Ling , Wei Yuanfeng , Tan Bowen , Wu Yongzhi , Yi Cheng , Liao Jinfeng
Published: October 2021

Background

As one of the leading threats for health among women worldwide, breast cancer has high morbidity and mortality. Surgical resection is the major clinical intervention for primary breast tumor, nevertheless high local recurrence risk and breast tissue defect remain two main clinical dilemmas, seriously affecting survival and quality of life of patients.

Experimental

We developed a thermoresponsive and injectable hybrid hydrogel platform (IR820/Mgel) by integration of co-loaded porous microspheres (MPs) and IR820 for preventing postoperative recurrence of breast cancer via photothermal therapy and promoting subsequent breast reconstruction.

Results

Our results suggested that IR820/Mgel could quickly heated to more than 50.0 ℃ under NIR irradiation, enabling killing effect on 4T1 cells in vitro and prevention effect on post-surgical tumor recurrence in vivo. In addition, the hydrogel platform was promising for its minimal invasion and capability of filling irregularly shaped defects after surgery, and the encapsulated MPs could help to increase the strength of gel to realize a long-term in situ function in vivo, and promoted the attachment and anchorage property of normal breast cells and adipose stem cells.

Conclusions

This photothermal hydrogel platform provides a practice paradigm for preventing locally recurrence of breast cancer and a potential option for reconstruction of breast defects.

Graphic abstract
Laennec’s approach for laparoscopic anatomical hemihepatectomy
Authors: Hu Wei , Zhang Gongming , Chen Meng , Zhong Chengcheng , Li Mingxu , Sun Xitai , Li Kai , Wang Zhong
Published: October 2021

Background

Laennec’s capsule has been found for about 200 years. However, laparoscopic anatomical right and left hemihepatectomy (LARH and LALH) using Laennec’s approach are rarely reported.

Methods

We retrospectively analyzed the technical details and the surgical outcomes of 15 patients who underwent LAH via Laennec’s approach between May 2017 and July 2020. The operation time, intraoperative blood loss, postoperative complications, and hospital stay were recorded and analyzed.

Results

Four of 15 patients were diagnosed with hepatic hemangioma, 2 had hepatolithiasis, and 9 patients had primary liver cancer. During the surgery, Laennec’s approach was used for LAH without conversion to open surgery. Four patients were treated with LARH, and 11 patients were cured with LALH. The mean age of the patients was 62.1 ± 6.5 years, and four were male. The mean operative time, blood loss, and length of the postoperative hospital stay were 193 ± 49 min, 247 ± 120 mL, and 8.7 ± 2.0 days, respectively. There was no incidence of postoperative bile leakage and bleeding. No mortality occurred. We also demonstrated that Laennec’s capsule does exist around the peripheral hepatic veins with histological confirmation.

Conclusions

Laennec’s approach is safe and feasible for LAH. Precise isolation of Laennec’s approach based on Laennec’s capsule helps to standardize the surgical techniques for laparoscopic anatomical hepatectomy.
EGF stimulates human trophoblast cell invasion by downregulating ID3-mediated KISS1 expression
Authors: Fang Lanlan , Gao Yibo , Wang Zhen , Li Yuxi , Yan Yang , Wu Ze , Cheng Jung-Chien , Sun Ying-Pu
Published: October 2021

Background

During pregnancy, trophoblast cell invasion needs to be finely controlled. Aberrant trophoblast cell invasion is associated with placental diseases. Epidermal growth factor (EGF) and its receptor, EGFR, are expressed in trophoblast cells. Although the pro-invasive effect of EGF on trophoblast cells has been reported, the underlying mechanism remains largely unknown.

Results

In the present study, we conducted an RNA sequencing (RNA-seq) to HTR-8/SVneo human trophoblast cells in response to EGF and identified KISS1 as a target gene of EGF. The human KISS1 gene encodes kisspeptin, also known as metastin, which can suppress tumor metastasis. Our results showed that EGF treatment downregulated KISS1 expression and secretion by activating the EGFR-mediated PI3K/AKT signaling pathway. In addition, the expression of inhibitor of DNA-binding protein 3 (ID3) was downregulated by EGF and that was required for the EGF-suppressed KISS1 expression. Functionally, transwell invasion assays demonstrated that EGF stimulated human trophoblast cell invasion by downregulating KISS1 expression. Preeclampsia (PE) is a placental disease characterized by insufficient trophoblast cell invasion. Our clinical results revealed that serum levels of EGF were downregulated while serum and placental levels of KISS1 were upregulated in PE patients.

Conclusions

This study demonstrates that downregulation of EGF can lead to poor trophoblast cell invasion by increasing KISS1 expression which subsequently contributes to the pathogenesis of PE.
Clinical and genetic characteristics of PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome
Authors: Zhang Dan , Su Gaixiu , Liu Yan , Lai Jianming
Published: October 2021

Objective

To summarise the clinical and genetic characteristics of three children with PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome.

Methods

This study retrospectively analysed the clinical and genetic data of three children with PAMI syndrome in our hospital between April 2018 and January 2020.

Results

One male and two female children were 6 years and 5 months, 8 years and 7 months, and 13 years and 3 months of age. All three patients had a recurrent blood trilineage hypoplasia and splenomegaly. Patient 1 had pyoderma gangrenosum, and Ludwig’s angina. Patient 2 had pyogenic arthritis, and pyoderma gangrenosum. Patient 3 had hepatomegaly, pyogenic arthritis, and pulmonary hypertension. Laboratory tests revealed that all three children had elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Patient 1: C-antineutrophilic cytoplasmic antibodies(c-ANCA), positive; antiglobulin test (Coombs), positive. Patient 2: blood zinc, 4.38 mg/L (elevated). Patient 3: Antinuclear antibodies (ANA), 1:100, β2 glycoprotein I, positive; Coombs test, positive; RF, 28.3 U/ml (elevated); C3, 0.77 g/L (decreased). Genetic testing showed that all 3 patients had PSTPIP1 c.748G > A (p.E250K) spontaneous heterozygous mutations, suggesting the diagnosis of PAMI syndrome. Patient 1 was treated with a combination of methylprednisolone and cyclosporine for 8 months. The patient did not develop new skin lesions. The blood count showed mild neutropenia. The spleen was considerably retracted and the CRP became normal. Patient 2 was treated with etanercept and methylprednisolone. The patient had no further arthralgias and pyoderma gangrenosum showed improvement. The spleen was smaller than before. White blood cells were shown to be approximately 2–3 × 109/L. The haematocrit, platelets, CRP, and AESR were normal. Patient 3 was treated with methylprednisolone, methotrexate, and infliximab 4 times. The patient’s joint symptoms disappeared gradually and the liver retracted markedly. The pulmonary artery pressure returned to normal. Moreover, Coombs test result was negative. CRP and AESR were lower than before.

Conclusion

PAMI syndrome can manifest as pyogenic arthritis, pyoderma gangrenosum, acne, and trilineage hypoplasia, as well as autoimmune diseases. Glucocorticoid and immunosuppressive therapy are partially effective and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing is helpful to confirm diagnosis.
Time-restricted feeding improves blood glucose and insulin sensitivity in overweight patients with type 2 diabetes: a randomised controlled trial
Authors: Che Tingting , Yan Cheng , Tian Dingyuan , Zhang Xin , Liu Xuejun , Wu Zhongming
Published: October 2021

Background

Time-restricted feeding is an emerging dietary intervention that is becoming increasingly popular. There are, however, no randomised clinical trials of time-restricted feeding in overweight patients with type 2 diabetes. Here, we explored the effects of time-restricted feeding on glycaemic regulation and weight changes in overweight patients with type 2 diabetes over 12 weeks.

Methods

Overweight adults with type 2 diabetes (n = 120) were randomised 1:1 to two diet groups: time-restricted feeding (n = 60) or control (n = 60). Sixty patients participated in a 10-h restricted feeding treatment program (ad libitum feeding from 8:00 to 18:00 h; fasting between 18:00 and 8:00 h) for 12 weeks.

Results

Haemoglobin A1c and body weight decreased in the time-restricted feeding group (− 1.54% ± 0.19 and − 2.98 ± 0.43 kg, respectively) relative to the control group over 12 weeks (p < 0.001). Homeostatic model assessment of β-cell function and insulin resistance changed in the time-restricted feeding group (0.73 ± 0.21, p = 0.005; − 0.51 ± 0.08, p = 0.02, respectively) compared with the control group. The medication effect score, SF-12 score, and the levels of triglycerides, total cholesterol and low-density lipoprotein cholesterol were improved in the time-restricted feeding group (− 0.66 ± 0.17, p = 0.006; 5.92 ± 1.38, p < 0.001; − 0.23 ± 0.08 mmol/L, p = 0.03; − 0.32 ± 0.07 mmol/L, p = 0.01; − 0.42 ± 0.13 mmol/L, p = 0.02, respectively) relative to the control group. High-density lipoprotein cholesterol was not significantly different between the two groups.

Conclusion

These results suggest that 10-h restricted feeding improves blood glucose and insulin sensitivity, results in weight loss, reduces the necessary dosage of hypoglycaemic drugs and enhances quality of life. It can also offer cardiovascular benefits by reducing atherosclerotic lipid levels.

Trial registration: This study was registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-15006371).
Adjuvant therapy for retroperitoneal sarcoma: a meta-analysis
Authors: Li Xiangji , Wu Tong , Xiao Mengmeng , Wu Shanshan , Min Li , Luo Chenghua
Published: October 2021

Background

Adjuvant therapy is a promising treatment to improve the prognosis of cancer patients, however, the evidence base driving recommendations for adjuvant radiotherapy (ART) or chemotherapy (ACT) in retroperitoneal sarcomas (RPS) primarily hinges on observational data. The aim of this study was to evaluate the effectiveness of adjuvant therapy in the management of RPS patients.

Methods

We searched PubMed, Web of Science, Embase, ASCO Abstracts, and Cochrane Library for comparative studies (until December 2020) of adjuvant therapy versus surgery alone. Data on the following endpoints were evaluated: overall survival (OS), local recurrence (LR), recurrence-free survival (RFS), and metastasis-free survival (MFS). Data were summarized as hazard ratios (HR) with 95% confidence intervals (CI). Risk of bias of studies was assessed with Begg’s and Egger’s tests.

Results

A total of 15 trials were eligible, including 9281 adjuvant therapy and 21,583 surgery alone cases (20 studies for OS, six studies for RFS, two studies for LR, and two studies for MFS). Meta-analysis showed that ART was associated with distinct advantages as compared to surgery alone, including a longer OS (HR = 0.80, P < 0.0001), a longer RFS (HR = 0.61, P = 0.0002), and a lower LR (HR = 0.31, P = 0.005). However, this meta-analysis failed to demonstrate a benefit of ACT for RPS patients, including OS (HR = 1.11, P = 0.19), RFS (HR = 1.30, P = 0.09) and MFS (HR = 0.69, P = 0.09). In the sensitivity analysis, ACT was associated with a worse OS (HR = 1.19, P = 0.0002). No evidence of publication bias was observed.

Conclusions

Overall, the quality of the evidence was moderate for most outcomes. The evidence supports that ART achieved a generally better outcome as compared to surgery alone.
Clinicopathologic significance and prognostic value of circRNAs in osteosarcoma: a systematic review and meta-analysis
Authors: Zhong Jingyu , Zhang Guangcheng , Yao Weiwu
Published: October 2021

Background

Osteosarcoma is the most prevalent malignant osseous sarcoma in children and adolescents, whose prognosis is still relatively poor nowadays. Recent studies have shown the critical function and potential clinical applications of circular RNAs (circRNAs) in osteosarcoma. Our review aimed to perform an updated meta-analysis to explore their clinicopathologic significance and prognostic value.

Methods

The structured literature was conducted via eight electronic databases and four gray literature sources until 20 Feb 2021 to identify eligible studies. The data was extracted directly from the articles or reconstructed based on Kaplan-Meier curves. The Newcastle-Ottawa Scale (NOS) tool was used to assess study quality. The clinicopathologic significance of circRNAs was measured through odds ratios (ORs) and their 95% confidence intervals (CIs), while the prognostic value was evaluated through hazard ratios (HRs) and their 95% CIs of overall survival (OS) and disease-free survival (DFS). Heterogeneity and publication bias were assessed. Sensitivity analyses were conducted. Subgroup analyses were performed according to study characteristics. An additional analysis was performed to investigate the relation between circ_0002052 and osteosarcoma.

Results

Fifty-two studies were identified, in which 38 on clinicopathologic features and 36 on survival prognosis were included in quantitative analysis. The overall study quality was moderate with a median NOS score of 5.5 stars (range 3 to 8). For clinicopathologic features, dysregulated circRNAs were related to larger tumor size (OR 2.122, 95%CI 1.418–3.175), advanced clinical stage (OR 2.847, 95%CI 2.059–3.935), and present of metastasis (OR 2.630, 95%CI 1.583–4.371). For chemotherapy, dysregulated circRNAs suggest a better response (OR 0.443, 95%CI 0.231–0.849), but a higher probability of resistance (OR 9.343, 95%CI 5.352–16.309). For survival prognosis, dysregulated circRNAs were significantly correlated with poor OS (HR 2.437, 95%CI 2.224–2.670) and DFS (HR 2.125, 95%CI 1.621–2.786). The results did not show differences among subgroups. Higher circ_0002052 expression showed a relation with poor OS (HR 3.197, 95%CI 2.054–4.976).

Conclusions

Our review demonstrated that abnormally expressed circRNAs have a relation with advanced clinicopathologic features and better response, but a higher probability of resistance and poor survival prognosis in osteosarcoma patients. However, more studies are encouraged to provide more robust evidence to translate circRNAs into clinical practice.

Trial registration

PROSPERO ID: CRD42021235031
Allelic and dosage effects of NHS in X-linked cataract and Nance–Horan syndrome: a family study and literature review
Authors: Miller Caroline , Gertsen Benjamin G. , Schroeder Audrey L. , Fong Chin-To , Iqbal M. Anwar , Zhang Bin
Published: October 2021

Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder caused by mutation in the NHS gene on chromosome Xp22.13. (OMIM 302350). Classic NHS manifested in males is characterized by congenital cataracts, dental anomalies, dysmorphic facial features and occasionally intellectual disability. Females typically have a milder presentation. The majority of reported cases of NHS are the result of nonsense mutations and small deletions. Isolated X-linked congenital cataract is caused by non-recurrent rearrangement-associated aberrant NHS transcription. Classic NHS in females associated with gene disruption by balanced X-autosome translocation has been infrequently reported. We present a familial NHS associated with translocation t(X;19) (Xp22.13;q13.1). The proband, a 28-year-old female, presented with intellectual disability, dysmorphic features, short stature, primary amenorrhea, cleft palate, and horseshoe kidney, but no NHS phenotype. A karyotype and chromosome microarray analysis (CMA) revealed partial monosomy Xp/partial trisomy 19q with the breakpoint at Xp22.13 disrupting the NHS gene. Family history revealed congenital cataracts and glaucoma in the patient’s mother, and congenital cataracts in maternal half-sister and maternal grandmother. The same balanced translocation t(X;19) was subsequently identified in both the mother and maternal half-sister, and further clinical evaluation of the maternal half-sister made a diagnosis of NHS. This study describes the clinical implication of NHS gene disruption due to balanced X-autosome translocations as a unique mechanism causing Nance–Horan syndrome, refines dose effects of NHS on disease presentation and phenotype expressivity, and justifies consideration of karyotype and fluorescence in situ hybridization (FISH) analysis for female patients with familial NHS if single-gene analysis of NHS is negative.
Mutant NPM1-regulated lncRNA HOTAIRM1 promotes leukemia cell autophagy and proliferation by targeting EGR1 and ULK3
Authors: Jing Yipei , Jiang Xueke , Lei Li , Peng Meixi , Ren Jun , Xiao Qiaoling , Tao Yao , Tao Yonghong , Huang Junpeng , Wang Lu , Tang Yuting , Yang Zailin , Yang Zesong , Zhang Ling
Published: October 2021

Background

Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1), which displays a distinct long noncoding RNA (lncRNA) expression profile, has been defined as a unique subgroup in the new classification of myeloid neoplasms. However, the biological roles of key lncRNAs in the development of NPM1-mutated AML are currently unclear. Here, we aimed to investigate the functional and mechanistic roles of the lncRNA HOTAIRM1 in NPM1-mutated AML.

Methods

The expression of HOTAIRM1 was analyzed with a public database and further determined by qRT-PCR in NPM1-mutated AML samples and cell lines. The cause of upregulated HOTAIRM1 expression was investigated by luciferase reporter, chromatin immunoprecipitation and ubiquitination assays. The functional role of HOTAIRM1 in autophagy and proliferation was evaluated using western blot analysis, immunofluorescence staining, a Cell Counting Kit-8 (CCK-8) assay, a 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay, flow cytometric analyses and animal studies. The action mechanism of HOTAIRM1 was explored through RNA fluorescence in situ hybridization, RNA pulldown and RNA immunoprecipitation assays.

Results

HOTAIRM1 was highly expressed in NPM1-mutated AML. High HOTAIRM1 expression was induced in part by mutant NPM1 via KLF5-dependent transcriptional regulation. Importantly, HOTAIRM1 promoted autophagy and proliferation both in vitro and in vivo. Mechanistic investigations demonstrated that nuclear HOTAIRM1 promoted EGR1 degradation by serving as a scaffold to facilitate MDM2-EGR1 complex formation, while cytoplasmic HOTAIRM1 acted as a sponge for miR-152-3p to increase ULK3 expression.

Conclusions

Taken together, our findings identify two oncogenic regulatory axes in NPM1-mutated AML centered on HOTAIRM1: one involving EGR1 and MDM2 in the nucleus and the other involving the miR-152-3p/ULK3 axis in the cytoplasm. Our study indicates that HOTAIRM1 may be a promising therapeutic target for this distinct leukemia subtype.
Global properties of regulatory sequences are predicted by transcription factor recognition mechanisms
Authors: Patel Zain M. , Hughes Timothy R.
Published: October 2021

Background

Mammalian genomes contain millions of putative regulatory sequences, which are delineated by binding of multiple transcription factors. The degree to which spacing and orientation constraints among transcription factor binding sites contribute to the recognition and identity of regulatory sequence is an unresolved but important question that impacts our understanding of genome function and evolution. Global mechanisms that underlie phenomena including the size of regulatory sequences, their uniqueness, and their evolutionary turnover remain poorly described.

Results

Here, we ask whether models incorporating different degrees of spacing and orientation constraints among transcription factor binding sites are broadly consistent with several global properties of regulatory sequence. These properties include length, sequence diversity, turnover rate, and dominance of specific TFs in regulatory site identity and cell type specification. Models with and without spacing and orientation constraints are generally consistent with all observed properties of regulatory sequence, and with regulatory sequences being fundamentally small (~ 1 nucleosome). Uniqueness of regulatory regions and their rapid evolutionary turnover are expected under all models examined. An intriguing issue we identify is that the complexity of eukaryotic regulatory sites must scale with the number of active transcription factors, in order to accomplish observed specificity.

Conclusions

Models of transcription factor binding with or without spacing and orientation constraints predict that regulatory sequences should be fundamentally short, unique, and turn over rapidly. We posit that the existence of master regulators may be, in part, a consequence of evolutionary pressure to limit the complexity and increase evolvability of regulatory sites.
Network propagation-based prioritization of long tail genes in 17 cancer types
Authors: Mohsen Hussein , Gunasekharan Vignesh , Qing Tao , Seay Montrell , Surovtseva Yulia , Negahban Sahand , Szallasi Zoltan , Pusztai Lajos , Gerstein Mark B.
Published: October 2021

Background

The diversity of genomic alterations in cancer poses challenges to fully understanding the etiologies of the disease. Recent interest in infrequent mutations, in genes that reside in the “long tail” of the mutational distribution, uncovered new genes with significant implications in cancer development. The study of cancer-relevant genes often requires integrative approaches pooling together multiple types of biological data. Network propagation methods demonstrate high efficacy in achieving this integration. Yet, the majority of these methods focus their assessment on detecting known cancer genes or identifying altered subnetworks. In this paper, we introduce a network propagation approach that entirely focuses on prioritizing long tail genes with potential functional impact on cancer development.

Results

We identify sets of often overlooked, rarely to moderately mutated genes whose biological interactions significantly propel their mutation-frequency-based rank upwards during propagation in 17 cancer types. We call these sets “upward mobility genes” and hypothesize that their significant rank improvement indicates functional importance. We report new cancer-pathway associations based on upward mobility genes that are not previously identified using driver genes alone, validate their role in cancer cell survival in vitro using extensive genome-wide RNAi and CRISPR data repositories, and further conduct in vitro functional screenings resulting in the validation of 18 previously unreported genes.

Conclusion

Our analysis extends the spectrum of cancer-relevant genes and identifies novel potential therapeutic targets.
The effect of irrigation on malaria vector bionomics and transmission intensity in western Ethiopia
Authors: Haileselassie Werissaw , Zemene Endalew , Lee Ming-Chieh , Zhong Daibin , Zhou Guofa , Taye Behailu , Dagne Alemayehu , Deressa Wakgari , Kazura James W. , Yan Guiyun , Yewhalaw Delenasaw
Published: October 2021

Background

Irrigation schemes may result in subsequent changes in malaria disease dynamics. Understanding the mechanisms and effects of irrigation on malaria vector bionomics and transmission intensity is essential to develop new or alternative surveillance and control strategies to reduce or control malaria risk. This study was designed to assess the effect of rice irrigation on malaria vector bionomics and transmission intensity in the Gambella Region, Ethiopia.

Methods

Comparative cross-sectional study was conducted in Abobo District of the Gambella Region, Ethiopia. Accordingly, clusters (kebeles) were classified into nearby and faraway clusters depending on their proximity to the irrigation scheme. Adult mosquito survey was conducted in February, August and November 2018 from three nearby and three faraway clusters using Centers for Disease Control and Prevention (CDC) light traps (LTs). During the November survey, human landing catch (HLC) and pyrethrum spray catch (PSC) were also conducted. The collected mosquitoes were morphologically identified to species and tested for Plasmodium infection using circumsporozoite protein enzyme-linked immunosorbent assay (CSP-ELISA). Furthermore, species-specific polymerase chain reaction (PCR) was performed to identify member species of the Anopheles gambiae complex. Chi-square and t-tests were used to analyze the data using the SPSS version 20 software package.

Results

A total of 4319 female anopheline mosquitoes comprising An. gambiae sensu lato, An. funestus group, An. pharoensis, An. coustani complex and An. squamosus were collected. Overall, 84.5% and 15.5% of the anopheline mosquitoes were collected from the nearby and faraway clusters, respectively. Anopheles gambiae s.l. was the predominant (56.2%) anopheline species in the area followed by An. pharoensis (15.7%). The density of anopheline mosquitoes was significantly higher in the nearby clusters in both HLCs [t(3)  =  5.14, P  =  0.0143] and CDC LT catches [t(271.97)  =  7.446, P  <  0.0001). The overall sporozoite rate of anopheline species from the nearby clusters was 10-fold higher compared to the faraway clusters.

Conclusions

Significantly higher mosquito population density was observed in areas close to the irrigation sites. Sporozoite infection rate in the mosquito population was also markedly higher from the nearby clusters. Therefore, the irrigation scheme could increase the risk of malaria in the area.

Graphical abstract
Australian mosquito assemblages vary between ground and sub-canopy habitats
Authors: Sebayang Boni F. , Russell Tanya L. , Staunton Kyran M. , Townsend Michael , Paton Christopher , Lehmann Tovi , Burkot Thomas R.
Published: October 2021

Background

The surveillance and control of mosquito-borne diseases is dependent upon understanding the bionomics and distribution of the vectors. Most studies of mosquito assemblages describe species abundance, richness and composition close to the ground defined often by only one sampling method. In this study, we assessed Australian mosquito species near the ground and in the sub-canopy using two traps baited with a variety of lures.

Methods

Mosquitoes were sampled using a 4 × 4 Latin square design at the Cattana Wetlands, Australia from February to April 2020, using passive box traps with octenol and carbon dioxide and three variations of a sticky net trap (unbaited, and baited with octenol or octenol and carbon dioxide). The traps were deployed at two different heights: ground level (≤ 1 m above the ground) and sub-canopy level (6 m above the ground).

Results

In total, 27 mosquito species were identified across the ground and sub-canopy levels from the different traps. The abundance of mosquitoes at the ground level was twofold greater than at the sub-canopy level. While the species richness at ground and sub-canopy levels was not significantly different, species abundance varied by the collection height.

Conclusions

The composition of mosquito population assemblages was correlated with the trap types and heights at which they were deployed.Coquillettidiaspecies, which prefer feeding on birds, were mainly found in the sub-canopy whereasAnopheles farauti,Aedes vigilaxandMansonia uniformis, which have a preference for feeding on large mammals, were predominantly found near the ground. In addition to trap height, environmental factors and mosquito bionomic characteristics (e.g. larval habitat, resting behaviour and host blood preferences) may explain the vertical distribution of mosquitoes. This information is useful to better understand how vectors may acquire and transmit pathogens to hosts living at different heights.

Graphical abstract
Epidemiological features and spatial–temporal distribution of visceral leishmaniasis in mainland China: a population-based surveillance study from 2004 to 2019
Authors: Guan Zhou , Chen Can , Huang Chenyang , Zhang Hongwei , Zhou Yiyi , Zhou Yuqing , Wu Jie , Zhou Zhengbin , Yang Shigui , Li Lanjuan
Published: October 2021

Background

Although visceral leishmaniasis (VL) was largely brought under control in most regions of China during the previous century, VL cases have rebounded in western and central China in recent decades. The aim of this study was to investigate the epidemiological features and spatial–temporal distribution of VL in mainland China from 2004 to 2019.

Methods

Incidence and mortality data for VL during the period 2004–2019 were collected from the Public Health Sciences Data Center of China and annual national epidemic reports of VL, whose data source was the National Diseases Reporting Information System. Joinpoint regression analysis was performed to explore the trends of VL. Spatial autocorrelation and spatial–temporal clustering analysis were conducted to identify the distribution and risk areas of VL transmission.

Results

A total of 4877 VL cases were reported in mainland China during 2004–2019, with mean annual incidence of 0.0228/100,000. VL incidence showed a decreasing trend in general during our study period (annual percentage change [APC] = −4.2564, 95% confidence interval [CI]: −8.0856 to −0.2677). Among mainly endemic provinces, VL was initially heavily epidemic in Gansu, Sichuan, and especially Xinjiang, but subsequently decreased considerably. In contrast, Shaanxi and Shanxi witnessed significantly increasing trends, especially in 2017–2019. The first-level spatial–temporal aggregation area covered two endemic provinces in northwestern China, including Gansu and Xinjiang, with the gathering time from 2004 to 2011 (relative risk [RR] = 13.91, log-likelihood ratio [LLR] = 3308.87, P < 0.001). The secondary aggregation area was detected in Shanxi province of central China, with the gathering time of 2019 (RR = 1.61, LLR = 4.88, P = 0.041). The epidemic peak of October to November disappeared in 2018–2019, leaving only one peak in March to May.

Conclusions

Our findings suggest that VL is still an important endemic infectious disease in China. Epidemic trends in different provinces changed significantly and spatial–temporal aggregation areas shifted from northwestern to central China during our study period. Mitigation strategies, including large-scale screening, insecticide spraying, and health education encouraging behavioral change, in combination with other integrated approaches, are needed to decrease transmission risk in areas at risk, especially in Shanxi, Shaanxi, and Gansu provinces.

Graphical abstract
Chemical composition and the insecticidal activity of Aeollanthus pubescens leaf essential oil against Anopheles gambiae sensu stricto
Authors: Bohounton Roméo Barnabé , Djogbénou Luc Salako , Djihinto Oswald Yédjinnavênan , Dedome Oronce Sedjro-Ludolphe , Sovegnon Pierre Marie , Barea Bruno , Adomou Aristide , Villeneuve Pierre , Tchobo Fidèle Paul
Published: October 2021

Background

The excessive use of synthetic insecticides is responsible for many cases of resistance in insects. Therefore, the use of natural molecules of ecological interest with insecticidal properties is an alternative approach to the use of synthetic insecticides. The aim of this study is to investigating the larvicidal and adulticidal activity and the chemical composition of the essential oil of Aeollanthus pubescens on the major malaria vector, Anopheles gambiae.

Methods

Three reference strains of Anopheles gambiae sensu stricto (Kisumu, Kiskdr and Acerkis) were used in this study. The leaves of A. pubescens were collected in southern Benin. The standard World Health Organisation (WHO) guidelines for larvicide evaluation were used, and the chemical composition of the essential oil was analysed by gas chromatography coupled to mass spectrometry. Adult mosquitoes of each strain were exposed to pieces of net coated with the essential oil for 3 min using the WHO cone bioassay method. Probit regression analysis was used to determine the concentrations that would kill 50 and 95% of each test population (LC50, LC95) and the knockdown time for 50 and 95% of each test population (KDT50, and KDT95). The difference between the mortality–dose regressions for the different strains was analysed using the likelihood ratio test (LRT). The log-rank test was performed to evaluate the difference in survival between the strains.

Results

A total of 14 components were identified, accounting for 98.3% of total oil content. The major components were carvacrol (51.1%), thymyle acetate (14.0%) and ɣ-terpinene (10.6%). The essential oil showed larvicidal properties on the Kisumu, Acerkis and Kiskdr strains, with LC50 of 29.6, 22.9 and 28.4 ppm, respectively. With pieces of netting treated at 165 µg/cm2, the KDT50 of both Acerkis (1.71 s; Z = 3.34, P < 0.001) and Kiskdr (2.67 s; Z = 3.49, P < 0.001) individuals were significantly lower than that of Kisumu (3.8 s). The lifespan of the three mosquito strains decreased to 1 day for Kisumu (χ2 = 99, df = 1, P < 0.001), 2 days for Acerkis (χ2 = 117, df = 1, P < 0.001) and 3 days for Kiskdr (χ2 = 96.9, df = 1, P < 0.001).

Conclusion

Our findings show that A. pubescens essential oil has larvicide and adulticide properties against the malaria vector An. gambiae sensu stricto, suggesting that this essential oil may be a potential candidate for the control of the resistant malaria-transmitting vectors.

Graphical Abstract
Genome-wide analyses of multiple obesity-related cytokines and hormones informs biology of cardiometabolic traits
Authors: Meeks Karlijn A. C. , Bentley Amy R. , Gouveia Mateus H. , Chen Guanjie , Zhou Jie , Lei Lin , Adeyemo Adebowale A. , Doumatey Ayo P. , Rotimi Charles N.
Published: October 2021

Background

A complex set of perturbations occur in cytokines and hormones in the etiopathogenesis of obesity and related cardiometabolic conditions such as type 2 diabetes (T2D). Evidence for the genetic regulation of these cytokines and hormones is limited, particularly in African-ancestry populations. In order to improve our understanding of the biology of cardiometabolic traits, we investigated the genetic architecture of a large panel of obesity- related cytokines and hormones among Africans with replication analyses in African Americans.

Methods

We performed genome-wide association studies (GWAS) in 4432 continental Africans, enrolled from Ghana, Kenya, and Nigeria as part of the Africa America Diabetes Mellitus (AADM) study, for 13 obesity-related cytokines and hormones, including adipsin, glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), interleukin-1 receptor antagonist (IL1-RA), interleukin-6 (IL-6), interleukin-10 (IL-10), leptin, plasminogen activator inhibitor-1 (PAI-1), resistin, visfatin, insulin, glucagon, and ghrelin. Exact and local replication analyses were conducted in African Americans (n = 7990). The effects of sex, body mass index (BMI), and T2D on results were investigated through stratified analyses.

Results

GWAS identified 39 significant (P value < 5 × 10−8) loci across all 13 traits. Notably, 14 loci were African-ancestry specific. In this first GWAS for adipsin and ghrelin, we detected 13 and 4 genome-wide significant loci respectively. Stratified analyses by sex, BMI, and T2D showed a strong effect of these variables on detected loci. Eight novel loci were successfully replicated: adipsin (3), GIP (1), GLP-1 (1), and insulin (3). Annotation of these loci revealed promising links between these adipocytokines and cardiometabolic outcomes as illustrated by rs201751833 for adipsin and blood pressure and locus rs759790 for insulin level and T2D in lean individuals.

Conclusions

Our study identified genetic variants underlying variation in multiple adipocytokines, including the first loci for adipsin and ghrelin. We identified population differences in variants associated with adipocytokines and highlight the importance of stratification for discovery of loci. The high number of African-specific loci detected emphasizes the need for GWAS in African-ancestry populations, as these loci could not have been detected in other populations. Overall, our work contributes to the understanding of the biology linking adipocytokines to cardiometabolic traits.
Chronic intracranial subdural hematoma after spinal anesthesia for a cesarean section: a case report
Authors: Bekele Delayehu , Bayable Mehari , Bedane Alemayehu
Published: October 2021

Background

Subdural hematoma is a rare, potentially devastating, yet curable complication of spinal anesthesia. Differentiation between post-dural puncture headache and subdural hematoma can be difficult, resulting in a delay in diagnosis.

Case presentation

We present a 28-year-old Ethiopian female patient who underwent elective cesarean section under spinal anesthesia and returned to the emergency department after 1 month with a worsening headache. Brain computed tomography revealed a chronic subdural hematoma with a significant midline shift. The patient recovered completely after surgical evacuation.

Conclusions

A high index of suspicion and close attention to the pattern and characteristics of the headache, coupled with a meticulous neurologic examination and neuroimaging, can help to achieve timely diagnosis of this serious entity. Investigation with head computed tomography or magnetic resonance imaging is vital.
An efficient population-based multi-objective task scheduling approach in fog computing systems
Authors: Movahedi Zahra , Defude Bruno , Hosseininia Amir mohammad
Published: October 2021

With the rapid development of Internet of Things (IoT) technologies, fog computing has emerged as an extension to the cloud computing that relies on fog nodes with distributed resources at the edge of network. Fog nodes offer computing and storage resources opportunities to resource-less IoT devices which are not capable to support IoT applications with computation-intensive requirements. Furthermore, the closeness of fog nodes to IoT devices satisfies the low-latency requirements of IoT applications. However, due to the high IoT task offloading requests and fog resource limitations, providing an optimal task scheduling solution that considers a number of quality metrics is essential. In this paper, we address the task scheduling problem with the aim of optimizing the time and energy consumption as two QoS parameters in the fog context. First, we present a fog-based architecture for handling the task scheduling requests to provide the optimal solutions. Second, we formulate the task scheduling problem as an Integer Linear Programming (ILP) optimization model considering both time and fog energy consumption. Finally, we propose an advanced approach called Opposition-based Chaotic Whale Optimization Algorithm (OppoCWOA) to enhance the performance of the original WOA for solving the modelled task scheduling problem in a timely manner. The efficiency of the proposed OppoCWOA is shown by providing extensive simulations and comparisons with the original WOA and some existing meta-heuristic algorithms such as Artificial Bee Colony (ABC), Particle Swarm Optimization (PSO), and Genetic Algorithm (GA).