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

Efficiency of Polyphenol Extraction from Artificial Honey Using C18 Cartridges and Amberlite„ XAD-2 Resin: A Comparative Study

A comparative study of the extraction efficiency of nine known polyphenols [phenolic acids (benzoic acid, dihydroxybenzoic acid, gallic acid, trans-cinnamic acid, and vanillic acid) and flavonoids (naringenin, naringin, quercetin, and rutin)] was conducted by deliberately adding the polyphenols to an artificial honey solution and performing solid phase extraction (SPE). Two SPE methods were compared: one using Amberlite XAD-2 resin and another one using a C18 cartridge. A gradient high performance liquid chromatography system with an RP18 column and photodiode array detector was utilized to analyze the extracted polyphenols. The mean percent of recovery from the C18 cartridges was 74.2%, while that from the Amberlite XAD-2 resin was 43.7%. The recoveries of vanillic acid, naringin, and rutin were excellent (>90%); however, gallic acid was not obtained when C18 cartridges were used. Additionally, the reusability of Amberlite XAD-2 resin was investigated, revealing that the mean recovery of polyphenols decreased from 43.7% (1st extraction) to 29.3% (3rd extraction). It was concluded that although Amberlite XAD-2 resin yielded a higher number of compounds, C18 cartridges gave a better extraction recovery. The lower recovery seen for the Amberlite XAD-2 resin also cannot be compensated by repeated extractions due to the gradual decrease of extraction recovery when reused

Trigeminal Neuralgia, Glossopharyngeal Neuralgia, and Myofascial Pain Dysfunction Syndrome: An Update

Neuropathic pain is a common phenomenon that affects millions of people worldwide. Maxillofacial structures consist of various tissues that receive frequent stimulation during food digestion.The unique functions (masticatory process and facial expression) of the maxillofacial structure require the exquisite organization of both the peripheral and central nervous systems. Neuralgia is painful paroxysmal disorder of the head-neck region characterized by some commonly shared features such as the unilateral pain, transience and recurrence of attacks, and superficial and shock-like pain at a trigger point.These types of pain can be experienced after nerve injury or as a part of diseases that affect peripheral and central nerve function, or they can be psychological. Since the trigeminal and glossopharyngeal nerves innervate the oral structure, trigeminal and glossopharyngeal neuralgia are the most common syndromes following myofascial pain dysfunction syndrome. Nevertheless, misdiagnoses are common. The aim of this review is to discuss the currently available diagnostic procedures and treatment options for trigeminal neuralgia, glossopharyngeal neuralgia, and myofascial pain dysfunction syndrome

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

Towards Realistic Few-Shot Relation Extraction: A New Meta Dataset and Evaluation

We introduce a meta dataset for few-shot relation extraction, which includes two datasets derived from existing supervised relation extraction datasets NYT29 (Takanobu et al., 2019; Nayak and Ng, 2020) and WIKIDATA (Sorokin and Gurevych, 2017) as well as a few-shot form of the TACRED dataset (Sabo et al., 2021). Importantly, all these few-shot datasets were generated under realistic assumptions such as: the test relations are different from any relations a model might have seen before, limited training data, and a preponderance of candidate relation mentions that do not correspond to any of the relations of interest. Using this large resource, we conduct a comprehensive evaluation of six recent few-shot relation extraction methods, and observe that no method comes out as a clear winner. Further, the overall performance on this task is low, indicating substantial need for future research. We release all versions of the data, i.e., both supervised and few-shot, for future research

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