Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive investigation of the clinical significance of long non-coding RNA HOXA-AS2 in acute myeloid leukemia using genome-wide RNA sequencing dataset

Objective: The present study aimed to determine the prognostic value of HOXA cluster antisense RNA2 (HOXA-AS2) in acute myeloid leukemia (AML), and to explore its potential molecular mechanisms. We also screening of potential drugs targeting HOXA-AS2 in AML. Methods: The level 3 raw genome-wide RNA sequencing dataset of AML was download from The Cancer Genome Atlas (TCGA) Data Portal, and the potential molecular mechanisms and drugs prediction of HOXA-AS2 in AML were explored using multiple bioinformatics analysis approaches. Results: TCGA AML cohort dataset indicated that HOXA-AS2 was significantly up-regulated in AML bone marrow tissues, and high HOXA-AS2 expression was related to poor overall survival (log-rank P=0.0284, hazard ratio 1.640, 95% confidence interval 1.046-2.573). Functional enrichment of differentially expressed genes (DEGs) suggested that the difference in prognosis between AML patients with high- and low-HOXA-AS2 expression may be due to differences in biological processes and pathways, including cell adhesion, angiogenesis, mitogen-activated protein kinase, cell differentiation, and other biological processes, and phosphatidylinositol 3 kinase-protein kinase B and Wnt signaling pathways. We also screened out three potential HOXA-AS2-targeted therapeutic drugs for AML, megestrol, carmustine, and cefoxitin, based on these DEGs. Functional enrichment analysis of HOXA-AS2-co-expressed genes revealed that HOXA-AS2 may act a part in AML by regulating nuclear factor-κB transcription factor activity, DNA methylation, angiogenesis, apoptosis, cell migration, Toll-like receptor 4, and Wnt signaling pathways. Conclusion: Our findings suggest that HOXA-AS2 is up-regulated in the bone marrow in patients with AML, and may serve as a novel prognostic biomarker for AML.
Numerical simulation of the electrophoretic transport of a biopolymer through a synthetic nano-pore

We employed a hybrid approach to study numerically the translocation of a biopolymer through an artificial nano-pore driven by an external electric field in the presence of an explicit solvent. The motion of the polymer is simulated by the 3D Langevin dynamics technique. The hydrodynamic interactions (HI) between the polymer and the fluid are taken into account by the lattice Boltzmann equation. Our polymer chain model representing the double-stranded DNA was first validated by comparing the diffusion coefficient obtained from the numerical results with the experimental and theoretical results. Then, we conducted numerical simulations of the biopolymer's translocation process by applying a theoretical formula for the net electrophoretic force acting on the part of the polymer residing in the pore. We compared quantitatively the translocation times and the velocities of different DNA lengths with the corresponding experimental results. Our simulation results are in good agreement with the experimental ones when the HI are considered explicitly.
New-onset acute rapidly deteriorating case of calciphylaxis after open heart surgery: a case report

Abstract Background Calciphylaxis is a rare life-threatening condition that is characterized by calcification of small blood vessels and soft tissues. This condition is classically described in uraemic patients with end-stage renal failure who are on dialysis or had previous renal transplant. It has also been reported in non-uraemic patients and those who are on warfarin therapy. It is typically associated with high calcium/phosphorus product. Patients classically present with painful skin lesion that evolve into painful ulcers. There are multiple risk factors that were reported to trigger or worsen calciphylaxis. Treatment is a multidisciplinary approach that involves elimination of risk factors, wound management, pain control, and optimization of calcium/phosphorus metabolism. Reported mortality rates are very high especially in the uraemic group. Case summary Here we present a case of a patient, who is on chronic renal dialysis for stage renal failure, who underwent mechanical mitral valve replacement and tricuspid valve repair. In the perioperative period, she was exposed to multiple risk factors that are known to potentially trigger prophylaxis. In the early postoperative period, she developed new-onset rapidly deteriorating skin lesions and the histopathological diagnosis confirmed calciphylaxis. Her treatment plan included pain control, frequent wound care, and optimization of nutritional and metabolic status. Discussion Calciphylaxis is a very serious condition that is usually associated with poor outcome. In this case, we discuss the unusual presentation of this condition with particular emphasis on the multiple perioperative risk factors that can potentially trigger the onset of calciphylaxis in postoperative cardiac patients. We also discuss the epidemiology, pathogenesis, diagnosis, histopathological findings, and different lines of treatment of this serious condition and the potential preventative strategies.
Long-Term Follow-up of β-Transfusion-Dependent Thalassemia (TDT) Normoglycemic Patients with Reduced Insulin Secretion to Oral Glucose Tolerance Test (OGTT): A Pilot Study

Objective To study the endocrine pancreas’ function in transfusion-dependent β-thalassemia (β-TDT) patients with a normal glucose tolerance test (NGT) and hypoinsulinemia. In addition, the prospective long–term follow-up using an annual oral glucose tolerance test (OGTT) to detect any abnormality of glucose metabolism. Patients and methods Seven β-TDT patients (mean age 22.4 ± 4.2 years) with NGT and inadequate insulin response (hypoinsulinemia) to OGTT were referred for a second opinion to an Italian Centre. Results The first-phase insulin response (FPIR), expressed as the sum of 1 and 3 minutes insulin, to intravenous glucose tolerance test (IVGTT), was between the 1st and 3rd percentile in two patients and between the 3rd and 10th percentile in five. The results were not associated with β-cell autoimmunity. After 43 ± 26 months (range 11 – 80 months) of follow-up, two patients developed impaired glucose tolerance (IGT), three both IGT and impaired fasting glucose (IFG) and two overt diabetes mellitus (DM). Interestingly, the patients who developed DM had, at baseline, the lowest value of the insulinogenic index (IGI: 0.08 and 0.25), defined as the ratio of the increment of plasma insulin to plasma glucose during the first 30 minutes after OGTT. Moreover, a significant correlation was found between the IGI at baseline and at follow-up in the patients who developed IGT with or without IFG (R= 0.927; P: 0.023). A significant reduction of Matsuda insulin sensitivity index (ISIM) and Insulin Secretion-Sensitivity Index-2 (ISSI-2) was documented in the study cohort at the diagnosis of IFG, IGT, and DM. There was a significant inverse correlation between ISSI-2 and area under the curve plasma glucose (AUC-PG). Conclusions These data demonstrated, for the first time, progressive deterioration in glucose homeostasis in β-TDT subjects with NGT and hypoinsulinemia and that the ISSI-2 index may be a valuable parameter to identify patients at high risk for developing glucose dysregulation.
Use of Innovative SPECT Techniques in the Presurgical Evaluation of Patients with Nonlesional Extratemporal Drug-Resistant Epilepsy

Up to 30% of patients with epilepsy may not respond to antiepileptic drugs. Patients with drug-resistant epilepsy (DRE) should undergo evaluation for seizure onset zone (SOZ) localization to consider surgical treatment. Cases of drug-resistant nonlesional extratemporal lobe epilepsy (ETLE) pose the biggest challenge in localizing the SOZ and require multiple noninvasive diagnostic investigations before planning the intracranial monitoring (ICM) or direct resection. Ictal Single Photon Emission Computed Tomography (i-SPECT) is a unique functional diagnostic tool that assesses the SOZ using the localized hyperperfusion that occurs early in the seizure. Subtraction ictal SPECT coregistered to MRI (SISCOM), statistical ictal SPECT coregistered to MRI (STATISCOM), and PET interictal subtracted ictal SPECT coregistered with MRI (PISCOM) are innovative SPECT methods for the determination of the SOZ. This article comprehensively reviews SPECT and sheds light on its vital role in the presurgical evaluation of the nonlesional extratemporal DRE.
Interactions of Lipid Droplets with the Intracellular Transport Machinery

Historically, studies of intracellular membrane trafficking have focused on the secretory and endocytic pathways and their major organelles. However, these pathways are also directly implicated in the biogenesis and function of other important intracellular organelles, the best studied of which are peroxisomes and lipid droplets. There is a large recent body of work on these organelles, which have resulted in the introduction of new paradigms regarding the roles of membrane trafficking organelles. In this review, we discuss the roles of membrane trafficking in the life cycle of lipid droplets. This includes the complementary roles of lipid phase separation and proteins in the biogenesis of lipid droplets from endoplasmic reticulum (ER) membranes, and the attachment of mature lipid droplets to membranes by lipidic bridges and by more conventional protein tethers. We also discuss the catabolism of neutral lipids, which in part results from the interaction of lipid droplets with cytosolic molecules, but with important roles for both macroautophagy and microautophagy. Finally, we address their eventual demise, which involves interactions with the autophagocytotic machinery. We pay particular attention to the roles of small GTPases, particularly Rab18, in these processes.
Mental Health among Adults during the COVID-19 Pandemic Lockdown: A Cross-Sectional Multi-Country Comparison

Despite the global impact of COVID-19, studies comparing the effects of COVID-19 on population mental health across countries are sparse. This study aimed to compare anxiety and depression symptoms during the COVID-19 lockdown among adults from 11 countries and to examine their associations with country-level COVID-19 factors and personal COVID-19 exposure. A cross-sectional survey was conducted among adults (≥18 years) in 11 countries (Brazil, Bulgaria, China, India, Ireland, North Macedonia, Malaysia, Singapore, Spain, Turkey, United States). Mental health (anxiety, depression, resilient coping, hope) and other study data were collected between June–August 2020. Of the 13,263 participants, 62.8% were female and 51.7% were 18–34 years old. Participants living in Brazil had the highest anxiety and depression symptoms while participants living in Singapore had the lowest. Greater personal COVID-19 exposure was associated with increased anxiety and depression symptoms, but country-level COVID-19 factors were not. Higher levels of hope were associated with reduced anxiety and depression; higher levels of resilient coping were associated with reduced anxiety but not depression. Substantial variations exist in anxiety and depression symptoms across countries during the COVID-19 lockdown, with personal COVID-19 exposure being a significant risk factor. Strategies that mitigate COVID-19 exposure and enhance hope and resilience may reduce anxiety and depression during global emergencies.
The Association of Glomerular Filtration Rate With Echocardiographic Parameters in Chronic Kidney Disease

Background Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in chronic kidney disease (CKD) patients. Aortic propagation velocity (APV), epicardial fat thickness (EFT) and carotid intima-media thickness (CIMT) measurements could provide additional information on assessing renal decline in CKD patients. The study aimed to evaluate EFT, AVP and CIMT in CKD patients and then investigate the association among those parameters. Methods A total of 170 CKD consecutive subjects were enrolled in the study. Patients were divided into five groups according to their estimated glomerular filtration rate (eGFR) values. Each patient underwent complete transthoracic echocardiography examination. APV, EFT and CIMT were measured for analyses. A multivariate linear regression model was used for analysis to determine the independent predictors of eGFR. Results The lowest APV was observed in stage IV-V, and the highest APV was observed in stage I-II (P < 0.001). Stage IV-V patients had the highest EFT and stage I-II patients had the lowest EFT (P < 0.001). Moreover, the lowest CIMT was observed in stage III, and the highest CIMT was observed in stage V (P < 0.001). eGFR was significantly and positively correlated with APV and negatively correlated with EFT and CIMT. In multivariate analyses, APV (odds ratio (OR): 0.289, P < 0.001), EFT (OR: -0.135, P < 0.001) and CIMT (OR: -0.388, P < 0.001) were independent predictors of eGFR. Conclusion We found that APV decreased, and EFT and CIMT increased as CKD progress. The present study suggests that APV, EFT and CIMT might be incorporated with the examination of CKD patients in daily practice.
A Cross-Sectional Study of Detection of Beta Globin (HBB) Haplotypes Among Beta Thalassemia Patients

Introduction Beta-thalassemia is among the most common monogenic disorders in the Arabian Peninsula. This study aimed to investigate the β-globin (HBB) haplotypes among β-thalassemia patients in Saudi cohort which have potential implications in understanding the clinical care of patients and population genetic factors associated with β-thalassemia. Methods We analyzed 60 β-thalassemia patients. Male/female distribution for β-thalassemia was 58.33%/41.66%. Results of hematological parameters and indices were obtained from the database. HBB haplotyping assay was performed for four specific loci of the HBB gene cluster using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results HBB haplotyping assay identified three novel patterns namely haplotype 1, haplotype 2, and haplotype 3 and three common African haplotypes including Benin, Senegal, and Cameron. The frequency of haplotype 1 was the highest among the studied samples (62%, n = 37) with 56.76% (n = 21) observed in males compared to 43.24% (n = 16) in females. This was followed by Senegal, haplotype 2, Benin and haplotype 3 with similar percentage, and Cameron haplotype with 18%, 12%, 3% and 2%, respectively. The relationship between these haplotypes and various hematological parameters was calculated and our study found no significant relationship (p-value >0.05). Conclusion Our study indicated the importance of finding out types of β-globin haplotypes as novel types being discovered. Though no statistically significant association was identified among all the haplotypes in terms of hematological parameters, Cameroon or Benin haplotypes had the mildest form because they have the highest means among all parameters. Further studies need to be carried out on a larger population to detect the frequency of each specific mutation in each haplotype among β-thalassemia patients. This would help to re-address the question of the origin(s) of the β-thalassemia.
PES inhibits human-inducible Hsp70 by covalent targeting of cysteine residues in the substrate-binding domain

Hsp70 proteins are a family of ancient and conserved chaperones. They play important roles in vital cellular processes, such as protein quality control and the stress response. Hsp70 proteins are a potential drug target for treatment of disease, particularly cancer. PES (2-phenylethynesulfonamide or pifithrin-μ) has been reported to be an inhibitor of Hsp70. However, the mechanism of PES inhibition is still unclear. In this study we found that PES can undergo a Michael addition reaction with Cys-574 and Cys-603 in the SBDα of human HspA1A (hHsp70), resulting in covalent attachment of a PES molecule to each Cys residue. We previously showed that glutathionylation of Cys-574 and Cys-603 affects the structure and function of hHsp70. In this study, PES modification showed similar structural and functional effects on hHsp70 to glutathionylation. Further, we found that susceptibility to PES modification is influenced by changes in the conformational dynamics of the SBDα, such as are induced by interaction with adjacent domains, allosteric changes, and mutations. This study provides new avenues for development of covalent inhibitors of hHsp70.
Atypical Microbiological Feature of Infectious Endophthalmitis on Jeju Island: A 10-Year Study at a Single Tertiary Referral Center

Background To analyze the microbiological causes of infectious endophthalmitis on an isolated island over ten years. Methods A retrospective review of the medical records of 49 eyes clinically diagnosed with infectious endophthalmitis between January 2009 and December 2018 was done. The subjects were recruited from a single tertiary referral center on Jeju Island. The baseline characteristics of all subjects were investigated, and a culture examination was performed. The isolated pathogens were analyzed to determine how their microbiological features differed from those in regions with different geographical conditions. Results Of the 49 eyes, causative microorganisms were identified in 27 eyes (55.1%). Bacteria were found in 24 cases and fungi in 3 cases. Among the exogenous causes, Staphylococcus species (Staphylococcus aureus, S. epidermidis, and S. hominis) were the most common pathogens (7 cases). Achromobacter xylosoxidans was the second most common causative pathogen (4 cases) followed by Moraxella species (3 cases). The most frequent endogenous origin was due to Klebsiella pneumoniae (6 cases). The subjects were divided into two groups according to the treatment results and analyzed for predisposing factors related to visual outcomes. The presence of diabetes mellitus (P = 0.038) and initial visual acuity (P ≤ 0.001) were significant predisposing factors for visual outcomes. Conclusion The causative microorganisms of endogenous endophthalmitis on Jeju Island were not different from those reported previously. However, isolated exogenous microorganisms were different from those reported in other studies from inland areas. A high incidence and atypical clinical features of Achromobacter xylosoxidans and Moraxella in exogenous endophthalmitis were observed, reflective of the distinct climatic features of Jeju Island: high humidity and temperature. Therefore, considering the causative microorganisms of exogenous endophthalmitis, it may be assumed that the causative microorganisms of exogenous endophthalmitis and its clinical manifestations differ according to the region.
Effect of Self-Controlled Exercise on Antioxidant Activity of Red Blood Cells and Functional Recovery of Limbs in Patients with Breast Cancer after Rehabilitation

Background: We aimed to investigate the effect of self-controlled exercise on the antioxidant activity of red blood cells and the recovery of limb function in patients with breast cancer after rehabilitation. Methods: Overall 130 breast cancer patients admitted to the First Affiliated Hospital of Zhengzhou University, China from Feb 2018 to Jan 2019 were divided into intervention group and control group. The control group received perioperative care and chemotherapy, the intervention group implemented a self-controlled exercise program. Indexes were compared between the two groups before intervention, 3 months and 6 months after intervention. Results: The activity of erythrocyte superoxide dismutase (SOD) in the intervention group was significantly increased in the first 3 months (P=0.030), and decreased from 3rd to 6th month (P=0.033). The glutathione peroxidase (GSH-Px) activity in the intervention group increased through the whole intervention period. The plasma malondialdehyde (MDA) in the intervention group was significantly decreased (P=0.029, 0.012). After intervention for 3 months and 6 months, the 6MND distances in the intervention group were significantly longer (P=0.001, 0.045). The average exercise time in the intervention group were significantly increased (P=0.004, 0.000). Conclusion: Self-controlled exercise can effectively improve the antioxidant ability of red blood cells in patients with breast cancer, improve the mobility of shoulder joints of the affected side and increase their exercise capacity, with good sustainability. It has positive effect on postoperative rehabilitation, could be used in long-term regular clinical work.
Extended Hückel Semi-Empirical Approach as an Efficient Method for Structural Defects Analysis in 4H-SiC

This paper presents an efficient method to calculate the influence of structural defects on the energy levels and energy band-gap for the 4H-SiC semiconductor. The semi-empirical extended Hückel method was applied to both ideal 4H-SiC crystal and different structures with defects like vacancies, stacking faults, and threading edge dislocations. The Synopsys QuatumATK package was used to perform the simulations. The results are in good agreement with standard density functional theory (DFT) methods and the computing time is much lower. This means that a structure with ca. 1000 atoms could be easily modeled on typical computing servers within a few hours of computing time, enabling fast and accurate simulation of non-ideal atomic structures.
Body Mass Index and Musculoskeletal Pain: A Cross-Sectional Study

Introduction With obesity reaching pandemic proportions, its detrimental influence on many health-related conditions has recently become a focus of research. Musculoskeletal (MSK) pain is one of several disorders associated with obesity. Materials and methods This study was designed to identify MSK pain in individuals with severe obesity, recruited from a specialized obesity clinic, and to evaluate the correlation between the MSK symptoms and some individual criteria. Results In 466 patients (342 females and 124 males), with a mean BMI of 42,77 ± 5.64 kg/m², 90,3% reported MSK pain. Severe pain was reported by 57,8% of female vs 26,6% of male patients. Female patients showed higher mean pain level when compared with males. Body sites with a higher prevalence of pain were: knee (63.5%), lumbar region (46.8%), hip (29%) and ankle (23%), with a predominance of severe pain. BMI have shown a positive correlation to numeric rating scale score in female participants in three body regions: shoulder (P = 0.010), knee (P = 0.042) and ankle (P = 0.024). Body sites with higher pain prevalence were especially in areas of increased mechanical load. Conclusions Understanding the relationship between obesity and pain may provide insights into preventive measures and therapeutic strategies for MSK pain. Persistent MSK pain is a significant problem in obese patients that can have a negative relationship with quality of life and function. This fact highlights the importance that patients with obesity may have access to interdisciplinary care, for the prevention and rehabilitation of MSK disorders. To further understand this association, more robust studies are needed.