Elucidation of clinical and laboratory features, comorbidity risks, treatment options and molecular pathophysiology of antiphospholipid syndrome (APS) patients

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by the presence of circulating antiphospholipid antibodies (aPLs) such as lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2-glycoprotein I (β2-GPI) antibodies to phospholipid binding proteins. Although the disease has been in existence for approximately 35 years, the diagnostic criteria, risk factors, pathogenesis, genetic aspects, treatment strategies are poorly understood and have yet to be fully developed. In this study, the clinical and laboratory features, genetic risk factors, comorbidity risks, molecular pathophysiology and optimal treatment strategy of APS patients are explored. Human peripheral blood mononuclear cell (PBMC)-derived high-quality and integrity RNA extraction and purification method was optimised (centrifugal speed: 14000 rpm + spin time: 75 seconds + DNase treatment + Ribolock RNase inhibitor + RNA clean-up) which could be used to send APS patients’ RNA for RNA-Seq. In quest of APS patients, two studies were conducted. Firstly, on a familial primary APS cases from Sarawak, Malaysia, patients however became seronegative following long warfarin therapy. Another one with APS subjects from Hospital Universiti Sains Malaysia (HUSM) were retrospectively investigated by exploring the clinical, laboratory and treatment strategies. High occurrence of pregnancy morbidity, as well as some unusual clinical features such as persistent dysfunction of liver and kidneys; menorrhagia and ovarian cyst were observed. The use of medium-intensity warfarin was successful in preventing thrombosis recurrence. Additionally, since theHUSM patients were unwilling to participate in this study, we were unable to send the RNA samples for RNA-Seq to BGI. A systematic review with bioinformatic analyses was conducted to identify the genetic risk factors in thrombotic APS subjects where 16 genes were significantly associated with thrombosis affecting mostly the blood coagulation pathway and the immune system related to APS. Overall, three systematic reviews and meta-analyses were conducted to determine the influence of aPLs in patients with migraine, epilepsy and dementia without autoimmune disease as compared to controls, where aPLs were significantly comorbid with the said manifestations. Therefore, the neurologic features were early clinical manifestations before the development of full-blown APS. A single Cochrane systematic review was developed to explore the optimum treatment strategy for thrombotic APS subjects, where, moderate-intensity warfarin was superior than high-intensity warfarin. Overall, a comprehensive study exploring the clinical and laboratory features, genetic risk factors, comorbidity risks, molecular pathophysiology and optimal treatment strategy of APS patients was successfully established. Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by the presence of circulating antiphospholipid antibodies (aPLs) such as lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2-glycoprotein I (β2-GPI) antibodies to phospholipid binding proteins. Although the disease has been in existence for approximately 35 years, the diagnostic criteria, risk factors, pathogenesis, genetic aspects, treatment strategies are poorly understood and have yet to be fully developed. In this study, the clinical and laboratory features, genetic risk factors, comorbidity risks, molecular pathophysiology and optimal treatment strategy of APS patients are explored. Human peripheral blood mononuclear cell (PBMC)-derived high-quality and integrity RNA extraction and purification method was optimised (centrifugal speed: 14000 rpm + spin time: 75 seconds + DNase treatment + Ribolock RNase inhibitor + RNA clean-up) which could be used to send APS patients’ RNA for RNA-Seq. In quest of APS patients, two studies were conducted. Firstly, on a familial primary APS cases from Sarawak, Malaysia, patients however became seronegative following long warfarin therapy. Another one with APS subjects from Hospital Universiti Sains Malaysia (HUSM) were retrospectively investigated by exploring the clinical, laboratory and treatment strategies. High occurrence of pregnancy morbidity, as well as some unusual clinical features such as persistent dysfunction of liver and kidneys; menorrhagia and ovarian cyst were observed. The use of medium-intensity warfarin was successful in preventing thrombosis recurrence. Additionally, since theHUSM patients were unwilling to participate in this study, we were unable to send the RNA samples for RNA-Seq to BGI. A systematic review with bioinformatic analyses was conducted to identify the genetic risk factors in thrombotic APS subjects where 16 genes were significantly associated with thrombosis affecting mostly the blood coagulation pathway and the immune system related to APS. Overall, three systematic reviews and meta-analyses were conducted to determine the influence of aPLs in patients with migraine, epilepsy and dementia without autoimmune disease as compared to controls, where aPLs were significantly comorbid with the said manifestations. Therefore, the neurologic features were early clinical manifestations before the development of full-blown APS. A single Cochrane systematic review was developed to explore the optimum treatment strategy for thrombotic APS subjects, where, moderate-intensity warfarin was superior than high-intensity warfarin. Overall, a comprehensive study exploring the clinical and laboratory features, genetic risk factors, comorbidity risks, molecular pathophysiology and optimal treatment strategy of APS patients was successfully established

Evaluating the efficacy of human dental pulp stem cells and scaffold combination for bone regeneration in animal models:A systematic review and meta-analysis

Abstract Introduction Human adult dental pulp stem cells (hDPSC) and stem cells from human exfoliated deciduous teeth (SHED) hold promise in bone regeneration for their easy accessibility, high proliferation rate, self-renewal and osteogenic differentiation capacity. Various organic and inorganic scaffold materials were pre-seeded with human dental pulp stem cells in animals, with promising outcomes in new bone formation. Nevertheless, the clinical trial for bone regeneration using dental pulp stem cells is still in its infancy. Thus, the aim of this systematic review and meta-analysis is to synthesise the evidence of the efficacy of human dental pulp stem cells and the scaffold combination for bone regeneration in animal bone defect models. Methodology This study was registered in PROSPERO (CRD2021274976), and PRISMA guideline was followed to include the relevant full-text papers using exclusion and inclusion criteria. Data were extracted for the systematic review. Quality assessment and the risk of bias were also carried out using the CAMARADES tool. Quantitative bone regeneration data of the experimental (scaffold + hDPSC/SHED) and the control (scaffold-only) groups were also extracted for meta-analysis. Results Forty-nine papers were included for systematic review and only 27 of them were qualified for meta-analysis. 90% of the included papers were assessed as medium to low risk. In the meta-analysis, qualified studies were grouped by the unit of bone regeneration measurement. Overall, bone regeneration was significantly higher (p < 0.0001) in experimental group (scaffold + hDPSC/SHED) compared to the control group (scaffold-only) (SMD: 1.863, 95% CI 1.121–2.605). However, the effect is almost entirely driven by the % new bone formation group (SMD: 3.929, 95% CI 2.612–5.246) while % BV/TV (SMD: 2.693, 95% CI − 0.001–5.388) shows a marginal effect. Dogs and hydroxyapatite-containing scaffolds have the highest capacity in % new bone formation in response to human DPSC/SHED. The funnel plot exhibits no apparent asymmetry representing a lack of remarkable publication bias. Sensitivity analysis also indicated that the results generated in this meta-analysis are robust and reliable. Conclusion This is the first synthesised evidence showing that human DPSCs/SHED and scaffold combination enhanced bone regeneration highly significantly compared to the cell-free scaffold irrespective of scaffold type and animal species used. So, dental pulp stem cells could be a promising tool for treating various bone diseases, and more clinical trials need to be conducted to evaluate the effectiveness of dental pulp stem cell-based therapies

Real-Time Detection and 3D Localization of Coronary Atherosclerosis Using a Microwave Imaging Technique: A Simulation Study

Obtaining the exact position of accumulated calcium on the inner walls of coronary arteries is critical for successful angioplasty procedures. For the first time to our knowledge, in this work, we present a high accuracy imaging of the inner coronary artery using microwaves for precise calcium identification. Specifically, a cylindrical catheter radiating microwave signals is designed. The catheter has multiple dipole-like antennas placed around it to enable a 360° field-of-view around the catheter. In addition, to resolve image ambiguity, a metallic rod is inserted along the axis of the plastic catheter. The reconstructed images using data obtained from simulations show successful detection and 3D localization of the accumulated calcium on the inner walls of the coronary artery in the presence of blood flow. Considering the space and shape limitations, and the highly lossy biological tissue environment, the presented imaging approach is promising and offers a potential solution for accurate localization of coronary atherosclerosis during angioplasty or other related procedures

Diagnostic accuracy of machine learning models on mammography in breast cancer classification:a meta-analysis

In this meta-analysis, we aimed to estimate the diagnostic accuracy of machine learning models on digital mammograms and tomosynthesis in breast cancer classification and to assess the factors affecting its diagnostic accuracy. We searched for related studies in Web of Science, Scopus, PubMed, Google Scholar and Embase. The studies were screened in two stages to exclude the unrelated studies and duplicates. Finally, 36 studies containing 68 machine learning models were included in this meta-analysis. The area under the curve (AUC), hierarchical summary receiver operating characteristics (HSROC) curve, pooled sensitivity and pooled specificity were estimated using a bivariate Reitsma model. Overall AUC, pooled sensitivity and pooled specificity were 0.90 (95% CI: 0.85–0.90), 0.83 (95% CI: 0.78–0.87) and 0.84 (95% CI: 0.81–0.87), respectively. Additionally, the three significant covariates identified in this study were country (p = 0.003), source (p = 0.002) and classifier (p = 0.016). The type of data covariate was not statistically significant (p = 0.121). Additionally, Deeks’ linear regression test indicated that there exists a publication bias in the included studies (p = 0.002). Thus, the results should be interpreted with caution

Efficacy and safety of isotonic and hypotonic intravenous maintenance fluids in hospitalised children:a systematic review and meta-analysis of randomised controlled trials

Hyponatraemia is a known complication in hospitalised children receiving maintenance intravenous fluid. Several studies have been published to investigate the efficacy and safety of intravenous fluids in children. However, there is still an ongoing debate regarding the ideal solution to be used in the paediatric population. Therefore, the aim of this meta-analysis was to investigate the safety and efficacy of administering isotonic versus hypotonic intravenous maintenance fluid in hospitalised children. An extensive search was undertaken on PubMed, Web of Science, Scopus, ScienceDirect, Google Scholar and Cochrane Library on 28 December 2020. Only randomised controlled trials (RCTs) were included. We used the random-effects model for all analyses. Risk ratio (RR) and mean difference with 95% confidence intervals (CIs) were used for dichotomous and continuous outcomes, respectively. The quality of each study was assessed using the Joanna Briggs Institute critical appraisal tool for RCTs. This study is registered with PROSPERO (CRD42021229067). Twenty-two RCTs with a total of 3795 participants were included. The studies encompassed surgical and medical patients admitted to intensive care unit as well as to general wards. We found that hypotonic fluid significantly increases the risk of hyponatremia at both ≤24 h (RR 0.34; 95% CI: 0.26–0.43, p 24 h (RR 0.48; 95% CI: 0.36–0.64, p 24 h (6.0% vs. 26.3%). There was no statistically significant difference in the risk of developing adverse outcomes between the two groups. Mean serum and urine sodium as well as serum osmolality/osmolarity was lower in the hypotonic group. Isotonic solution is protective against the development of hyponatraemia while hypotonic solution increases the risk of hyponatraemia

Prevalence of drug-resistant tuberculosis in Sudan:a systematic review and meta-analysis

Drug-resistant tuberculosis (DR-TB) is still one of the most critical issues impeding worldwide TB control efforts. The aim of this systematic review and meta-analysis was to give an updated picture of the prevalence of DR-TB in Sudan. A comprehensive systematic search was performed on four electronic databases (PubMed, Scopus, Web of Science and Google Scholar) to identify all published studies reporting prevalence data of DR-TB in Sudan. Sixteen eligible studies published during 2002–2020 were included. Using meta-analysis of proportions, the pooled prevalence of TB cases with resistance to any anti-TB drugs was 47.0% (95% CI: 35.5–58.6%). The overall prevalence of mono, multi, poly and extensive drug resistance were estimated to be 16.2% (95% CI: 9.0–23.4%), 22.8% (95% CI: 16.0–29.7%), 6.8% (95% CI: 0.5–13.0%) and 0.7% (95% CI: 0–2.1%), respectively. Considering any first-line anti-TB drugs, the resistance prevalence was highest for isoniazid (32.3%) and streptomycin (31.7%), followed by rifampicin (29.2%). In contrast, resistance against second-line drugs was reported for only two antibiotics, namely, ofloxacin (2.1%) and kanamycin (0.7%). Of note, the resistance profile of the previously treated patients was found to be remarkably high compared with the newly diagnosed TB patients. The relatively high prevalence estimation of anti-TB drug resistance warrants strengthening TB control and treatment strategies in Sudan

Prevalence of intestinal protozoan parasites among school children in Africa:a systematic review and meta-analysis

INTRODUCTION: Parasitic infections, especially intestinal protozoan parasites (IPPs) remain a significant public health issue in Africa, where many conditions favour the transmission and children are the primary victims. This systematic review and meta-analysis was carried out with the objective of assessing the prevalence of IPPs among school children in Africa. METHODS: Relevant studies published between January 2000 and December 2020 were identified by systematic online search on PubMed, Web of Science, Embase and Scopus databases without language restriction. Pooled prevalence was estimated using a random-effects model. Heterogeneity of studies were assessed using Cochrane Q test and I(2) test, while publication bias was evaluated using Egger’s test. RESULTS: Of the 1,645 articles identified through our searches, 46 cross-sectional studies matched our inclusion criteria, reported data from 29,968 school children of Africa. The pooled prevalence of intestinal protozoan parasites amongst African school children was 25.8% (95% CI: 21.2%-30.3%) with E. histolytica/ dispar (13.3%; 95% CI: 10.9%-15.9%) and Giardia spp. (12%; 95% CI: 9.8%-14.3%) were the most predominant pathogenic parasites amongst the study participants. While E. coli was the most common non-pathogenic protozoa (17.1%; 95% CI: 10.9%-23.2%). CONCLUSIONS: This study revealed a relatively high prevalence of IPPs in school children, especially in northern and western Africa. Thus, poverty reduction, improvement of sanitation and hygiene and attention to preventive control measures will be the key to reducing protozoan parasite transmission

Ruthenium complexes:an alternative to platinum drugs in colorectal cancer treatment

Colorectal cancer (CRC) is one of the intimidating causes of death around the world. CRC originated from mutations of tumor suppressor genes, proto-oncogenes and DNA repair genes. Though platinum (Pt)-based anticancer drugs have been widely used in the treatment of cancer, their toxicity and CRC cells’ resistance to Pt drugs has piqued interest in the search for alternative metal-based drugs. Ruthenium (Ru)-based compounds displayed promising anticancer activity due to their unique chemical properties. Ru-complexes are reported to exert their anticancer activities in CRC cells by regulating different cell signaling pathways that are either directly or indirectly associated with cell growth, division, proliferation, and migration. Additionally, some Ru-based drug candidates showed higher potency compared to commercially available Pt-based anticancer drugs in CRC cell line models. Meanwhile Ru nanoparticles coupled with photosensitizers or anticancer agents have also shown theranostic potential towards CRC. Ru-nanoformulations improve drug efficacy, targeted drug delivery, immune activation, and biocompatibility, and therefore may be capable of overcoming some of the existing chemotherapeutic limitations. Among the potential Ru-based compounds, only Ru (III)-based drug NKP-1339 has undergone phase-Ib clinical trials in CRC treatment