Miracle-dz/UniFAR-FTUs huggingface dataset:
Folding/unfolding kinetics of G-quadruplexes upstream of the P1 promoter of the human BCL-2 oncogene

The G-rich Pu39 region of the P1 promoter of the oncogene BCL-2, an apoptosis regulator, can fold into multiple G-quadruplex (G4) structures. Bcl2-2345 and Bcl2-1245 are two major G4 species forming with high thermal stability and distinct topologies in the Pu39 region, but their folding/unfolding kinetics have not yet been investigated. Here, we used magnetic tweezers to measure the mechanical stability and the folding/unfolding kinetics of the Bcl2-2345 and Bcl2-1245 G4 structures. We report that the hybrid-stranded Bcl2-2345 G4 had a lower mechanical stability than the parallel-stranded Bcl2-1245 G4. We observed that the Bcl2-2345 G4 is a kinetically favored structure, whereas the Bcl2-1245 G4, with a slow unfolding rate, may function as a kinetic barrier for transcription. We also determined that in addition to the Bcl2-2345 and Bcl2-1245 G4s, other stable DNA secondary structures, such as a hybrid-stranded Bcl2-1234 G4, can also form in the Pu39 sequence. The characterization of the folding/unfolding kinetics of specific G4s reported here sheds light on the participation of G4s during gene transcription and provides information for designing G4-targeting small molecules that could modulate BCL-2 gene expression.
Is gastroparesis a gastric disease?

Gastroparesis is a digestive syndrome characterized by delayed gastric emptying (GE) and by symptoms that are suggestive of gastroduodenal motor disorders. There are three grades of gastroparesis of increasing severity: (a) mild gastroparesis; (b) compensated gastroparesis; and (c) gastric failure. GE abnormalities are partially related to symptom type and severity, and other mechanisms may be involved.
Effect of Foreign Accent on Immediate Serial Recall

This study disentangled factors contributing to impaired memory for foreign-accented words – misperception and disruption of encoding. When native English and Cantonese-accented words were presented auditorily for serial recall (Experiment 1), intrusion errors for accented words were higher across all serial positions (SPs). Participants made more intrusion errors during auditory presentation than visual and auditory presentation, and more errors for accented words than native words. Lengthening the interstimulus intervals in Experiment 2 reduced intrusion, repetition, order, and omission errors in the middle and late SPs during accented word recall, suggesting that extra time is required for identification and encoding of accented words into memory. Analyses of the intrusions showed that a majority of them were misperceptions and sounded similar to the stimulus words. These findings suggest that effortful perceptual processing of accented speech can induce perceptual difficulty and interfere with downstream memory processes by exhausting the shared pool of working memory.
Clinical analysis of spinal stereotactic radiosurgery in the treatment of neurogenic tumors.

OBJECT In this study the authors sought to evaluate clinical outcomes after using stereotactic radiosurgery (SRS) to treat benign and malignant spinal neurogenic tumors. METHODS The authors reviewed a total of 66 procedures of spinal SRS performed between 2001 and 2013 for 110 tumors in 58 patients with spinal neurogenic tumors, which included schwannomas, neurofibromas, and malignant peripheral nerve sheath tumors (MPNSTs). The clinical and radiological findings were evaluated in patients with benign neurogenic tumors. For the 4 patients with MPNSTs, the authors reported overall survival and results of additional immunohistochemical staining to predict the survival difference among the patients. RESULTS Of the 92 benign neurogenic tumors, 65 tumors that were serially followed up using MRI after SRS showed significant change in mean tumor volume, from a mean of 12.0 ± 2.6 cm3 pre-SRS to 10.8 ± 2.5 cm3 post-SRS (p = 0.027), over an average of 44 months. The local control rate of benign neurogenic tumors was 95.4%. The 34 patients who presented with clinical symptoms of pain showed a significant symptomatic improvement. The initial mean visual analog scale (VAS) score was 6.0 and decreased dramatically to 1.0 after SRS during an average follow-up period of 10.9 months (median of 8.1 months). Although the proportions of transient swelling and loss of intramural enhancement were significantly different among the groups, there was no statistically significant correlation between those 2 factors and local tumor control (p = 0.253 and 0.067, respectively; Fisher's exact text). Cross-table analysis also indicated that there was no statistically significant relationship between groups with loss of intramural enhancement and transient swelling. The median survival of neurofibromatosis Type 1 (NF1)-related and sporadic MPNSTs was 1.13 and 5.8 years, respectively. Immunohistochemical results showed that S100 was expressed in a sporadic MPNST or neurofibroma, whereas topoisomerase-IIa was expressed in NF1-related MPNSTs. CONCLUSIONS SRS is an effective treatment modality for benign neurogenic tumors, while MPNSTs showed heterogeneity in their responses to SRS.
Strain Magnitude-Dependent Calcific Marker Expression in Valvular and Vascular Cells

Aortic valve disease and atherosclerosis tend to coexist in most patients with cardiovascular disease; however, the causes and mechanisms of disease development in heart valves are still not clearly understood. To understand the contributions of the magnitude of cyclic strain (5% hypotension, 10% physiological, and 15% hypertension) in calcification, we used a model system of tissue-engineered collagen gels containing human aortic smooth muscle cells and human aortic valvular interstitial cells, both isolated from noncalcific heart transplant tissue. The compacted collagen gels were cultured in osteogenic media for 3 weeks in a custom-designed bioreactor and all assessments were performed at the end of the culture period. The major finding of this study is that bone morphogenic protein (BMP)-2 and BMP-4 and transforming growth factor-β1 mRNA expression significantly changed in response to the magnitude of applied strain in valvular cells, while the lowest expression was observed for the representative physiological strain. On the other hand, mRNA expression in vascular cells did not vary in response to the magnitude of strain. Regarding BMP-2 and BMP-4 protein expression determined by immunostaining, trends were similar to mRNA expression in vascular and valvular cells, where only valvular cells showed a varied protein expression depending on the magnitude of the strain applied. Our results suggest that cellular differences exist between vascular and valvular cells in their response to altered levels of cyclic strain during calcification.
Biomechanical Evaluation of Spring Ligament Augmentation With the FiberTape Device in a Cadaveric Flatfoot Model

Background: The structural importance of the spring ligament complex in arch stability has been described. Furthermore, the pathology of this complex is often noted in patients with posterior tibial tendon dysfunction. The purpose of this biomechanical study was to evaluate spring ligament repair alone versus augmentation with the FiberTape device in a cadaveric flatfoot model. Methods: Eight paired, below-the-knee, cadaveric specimens underwent flatfoot creation and reconstruction. The experimental group received augmentation with FiberTape (InternalBrace). After potting, specimens were loaded statically to measure talonavicular contact pressures and flatfoot correction. Cyclic loading was performed in a stepwise fashion. Loading was performed at 1 Hz and 100 cycles, at 100-N intervals from 500 to 1800 N, with the Achilles tendon also loaded to simulate weightbearing in the postoperative period. Results: Control specimen analysis demonstrated failures of 8 of 8 (100%) spring ligament suture repairs, occurring through suture cut-through (5 specimens), suture fatigue and elongation (2), or knot failure (1). One of 8 (12.5%) FiberTape-augmented repairs failed after cyclic loading. The difference in number of repair failures was statistically significant between the 2 groups (P = .0014). Analysis revealed that at forces of 1600 N (P = .03) and 1700 N (P = .02) there were statistically significant differences between the FiberTape-augmented group and the control group, with a greater collapse in the lateral Meary talo–first metatarsal angle in the controls. There was no significant difference or abnormal increase in contact pressures of the talonavicular joint in both groups. Conclusion: FiberTape augmentation of the spring ligament appears biomechanically safe and effective under cyclic loading. Clinical relevance: Spring ligament augmentation with this device may be another biomechanically safe and reasonable treatment modality for surgeons during flatfoot reconstruction. It is possible that early protected weightbearing after these procedures may be performed.
Clinical Effectiveness of Cardiac Resynchronization and Implantable Cardioverter-Defibrillator Therapy in Men and Women With Heart Failure: Findings From IMPROVE HF

Background— Many clinical trials have demonstrated a benefit for cardiac resynchronization (CRT) and implantable cardioverter-defibrillator (ICD) therapies in patients with heart failure and reduced ejection fraction, yet questions have been raised with regard to the benefit of ICDs for women. The purpose of this study was to determine the clinical effectiveness of CRT and ICD therapy as a function of sex in outpatients with heart failure and reduced ejection fraction (⩽35%). Methods and Results— Data from the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) were analyzed by device status and sex among guideline-eligible patients for vital status (alive/dead) at 24 months. Multivariate generalized estimating equation analyses were conducted adjusting for baseline patient and practice characteristics. In the ICD/CRT-defibrillator (CRT-D) eligible cohort (n=7748), there were 5485 (71%) men and 2261 (29%) women. In the CRT-pacemaker (CRT-P)/CRT-D eligible cohort (n=1188), there were 824 (69%) men and 364 (31%) women. The clinical benefit associated with ICD/CRT-D therapy was similar in both men and women (men adjusted odds ratio, 0.71; 95% confidence interval, 0.57–0.87; P=0.0012; and women adjusted odds ratio, 0.65; 95% confidence interval, 0.49–0.85; P=0.0019). For CRT-P/CRT-D, the associated benefits showed no significant heterogeneity (men adjusted odds ratio, 0.59; 95% confidence interval, 0.33–1.06; P=0.0793; and women adjusted odds ratio, 0.44; 95% confidence interval, 0.22–0.90; P=0.0243). The device-by-sex interactions were not significant (P=0.4441 for CRT-P/CRT-D and P=0.5966 for ICD/CRT-D). Conclusions— The use of guideline-directed CRT and ICD therapy was associated with substantially reduced 24-month mortality in eligible men and women with heart failure and reduced ejection fraction. Device therapies should be offered to all eligible patients with heart failure, without modification based on sex.
Neonatal Outcomes Associated with Umbilical Cord Milking in Preterm Multiple Gestations

Abstract Objective Our aim was to evaluate the effect of umbilical cord milking on outcomes for preterm multiples. Study Design We implemented a policy of cord milking in neonates born at less than 30 weeks' gestation in September 2011. We compared cord milking in multiples with a historical cohort. Multivariable logistic regression models estimated the effect of cord milking on a composite neonatal adverse outcome. Secondary outcomes were hematocrit at birth, need for blood transfusion, and inotrope use. Results We identified 149 neonates (120 twins, 29 triplets), 51 historical controls, and 98 neonates with cord milking. Cord milking was associated with a lower rate of adverse composite neonatal outcome in univariable analysis (odds ratio [OR]: 0.36; 95% confidence interval [CI]: 0.15–0.84). However, in multivariable modeling, the effect was not significant (adjusted OR [aOR]: 0.54, 95% CI: 0.23–1.28). Hematocrit was 4.6 unit % (95% CI: 2–7.3) higher in the cord milking group, and cord milking was associated with a lower rate of blood transfusion (aOR: 0.28; 95% CI: 0.1–0.74; p = 0.01). There was no difference in inotrope administration. Conclusion Umbilical cord milking was not associated with a decrease in composite neonatal adverse outcome. However, we observed an increase in hematocrit and decreased need for blood transfusion in neonates with cord milking.
Effectiveness and Feasibility Associated with Switching to a Second or Third TNF Inhibitor in Patients with Psoriatic Arthritis: A Cohort Study from Southern Sweden

Objective. Because new modes of action for the treatment of psoriatic arthritis (PsA) are emerging, it is important to understand the use of switching to a second or third antitumor necrosis factor (anti-TNF) agent. This study investigated drug survival and treatment response rates of patients with PsA undergoing second- and third-line anti-TNF therapy. Methods. Patients with PsA were monitored in a prospective, observational study. Patients who switched anti-TNF therapy once (first-time switchers, n = 217) or twice (second-time switchers, n = 57) between January 2003 and March 2012 were studied. American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) good response at 3 and 6 months, as well as drug survival, were reported and further analyzed using the Cox and logistic regression models. Results. Median age for first-time switchers was 47 years and 42% were men. The corresponding values for second-time switchers were 48 years and 40% men. Three-month ACR20 Lund Efficacy Index (LUNDEX) response was achieved by 47% of first-time and 22% of second-time switchers; ACR50 LUNDEX rates were 21% and 14%, ACR70 LUNDEX rates were 12% and 2%, and EULAR good LUNDEX rates were 26% and 10%, respectively. Median drug survival time for patients switching anti-TNF for the first time was 64 months (95% CI 31–97) compared with 14 months (95% CI 5–23) for second-time switchers. Identified baseline predictor of ACR20 response to second-line treatment was the 28-joint Disease Activity Score values at baseline (OR 1.45, 95% CI 1.01–2.10), while higher Health Assessment Questionnaire scores predicted premature drug withdrawal (HR 1.60, 95% CI 1.03–2.48). Conclusion. Response rates of first-time anti-TNF switchers are moderate, while the inferior response rates of second-time switchers suggest other therapeutic options should be considered in this situation.
Microsatellite Diversity Delineates Genetic Relationships of Shia and Sunni Muslim Populations of Uttar Pradesh, India

Abstract In this study we characterize the genetic diversity and relationships between the Shia and Sunni Muslim populations of North India and geographically targeted neighboring and global populations. We examined a number of parameters of population genetic and forensic interest based on the allele frequencies from 15 autosomal STR loci (D8S1179, D21S11, D7S820, CSF1PO, D19S433, VWA, TPOX, D18S51, D3S1358, THO1, D13S317, D16S539, D2S1338, D5S818, and FGA). All the studied loci were consistent with Hardy-Weinberg equilibrium, except loci D18S51 and FGA for both Muslim populations, even after applying the Bonferroni correction. The combined power of exclusion and combined power of discrimination values for all 15 STR loci were 0.9999 and >0.99999, respectively, in both Muslim populations. Gene diversity values ranged from 0.6784 (TPOX) to 0.9027 (FGA) for Shia Muslims and from 0.7152 (CSF1PO) to 0.9120 (D18S51) for Sunni Muslims. The observed heterozygosity (Ho ) ranged from 0.5833 (D18S51) to 0.8595 (VWA) in Shia Muslims and from 0.6818 (CSF1PO) to 0.8333 (D21S11) in Sunni Muslims and was lower than the expected heterozygosity (He ) for 11 out of the 15 STRs typed. We analyzed the genetic affinities of the Shia and Sunni Muslim populations with their geographically closest neighboring North Indian, Middle Eastern, East Asian, and European populations using distance-based methods, including neighbor-joining trees and multidimensional scaling. In addition, we estimated the genetic contribution of the putative parental populations included in the analysis to the Shia and Sunni Muslim gene pool using admixture analysis. Although we observed a certain degree of genetic contribution from Iran to both Muslim populations, the results of the phylogenetic analyses based on autosomal STRs suggest genetic relatedness with some of the geographically closest neighboring Hindu religious populations.
FT Modulates Genome-Wide DNA-Binding of the bZIP Transcription Factor FD1[OPEN]

Genomic and biochemical analyses identify targets of the flowering time regulator FD at the genome-wide scale and shed light on the requirement for interaction with the florigen FLOWERING LOCUS T. The transition to flowering is a crucial step in the plant life cycle that is controlled by multiple endogenous and environmental cues, including hormones, sugars, temperature, and photoperiod. Permissive photoperiod induces the expression of FLOWERING LOCUS T (FT) in the phloem companion cells of leaves. The FT protein then acts as a florigen that is transported to the shoot apical meristem, where it physically interacts with the Basic Leucine Zipper Domain transcription factor FD and 14-3-3 proteins. However, despite the importance of FD in promoting flowering, its direct transcriptional targets are largely unknown. Here, we combined chromatin immunoprecipitation sequencing and RNA sequencing to identify targets of FD at the genome scale and assessed the contribution of FT to DNA binding. We further investigated the ability of FD to form protein complexes with FT and TERMINAL FLOWER1 through interaction with 14-3-3 proteins. Importantly, we observed direct binding of FD to targets involved in several aspects of plant development. These target genes were previously unknown to be directly related to the regulation of flowering time. Our results confirm FD as a central regulator of floral transition at the shoot meristem and provide evidence for crosstalk between the regulation of flowering and other signaling pathways, such as pathways involved in hormone signaling.
Delivering blended bioinformatics training in resource-limited settings: a case study on the University of Khartoum H3ABioNet node

Abstract Motivation Delivering high-quality distance-based courses in resource-limited settings is a challenging task. Besides the needed infrastructure and expertise, effective delivery of a bioinformatics course could benefit from hands-on sessions, interactivity and problem-based learning approaches. Results In this article, we discuss the challenges and best practices in delivering bioinformatics training in resource-limited settings taking the example of hosting and running a multiple-delivery online course, Introduction to Bioinformatics, that was developed by the H3ABioNet Education and Training working group and delivered in 27 remote classrooms across Africa in 2017. We take the case of the University of Khartoum classrooms. Believing that our local setting is similar to others in less-developed countries, we also reflect upon aspects like classroom environment and recruitment of students to maximize outcomes.
Multi-gene phylogeny of the genus Lobaria: Evidence of species-pair and allopatric cryptic speciation in East Asia.

PREMISE OF THE STUDY Accurate species delimitation has critical implications for ecological and conservation studies. The lichen genus Lobaria is widely distributed in old-growth forests. Particularly in East Asia, this genus includes many rare and poorly known taxa that are circumscribed as morpho- or chemospecies, as well as species-pairs. METHODS To critically examine the relationships between species identified via morphological and chemical criteria, phylogenetic species recognition (PSR) was applied to the genus Lobaria. Morphological and chemical patterns of 87 individuals were examined and three independent nuclear loci were sequenced. The East Asian L. meridionalis-group was additionally studied using split decomposition and haplotype network analysis. KEY RESULTS The genus Lobaria and most of its species were strongly supported statistically. Split decomposition and haplotype networks suggest complex evolutionary histories of species within the East Asian L. meridionalis-group. CONCLUSIONS Phylogenetic analyses confirmed the monophyly of the genus Lobaria, including L. anomala. Within Lobaria, three major clades were found. These clades associate with different photobionts and comprise 18 known species and 5 undescribed species. Several chemical compounds were found to be neither stable nor invariant characters. Some taxa of the L. meridionalis-group appear to be monophyletic but remain as allopatric cryptic species. In three clades, this study found evidence for diversification processes between isidiate and nonisidiate specimens (species-pair). These findings are discussed in the context of evolutionary hypotheses for speciation processes.
Malaria preventive behaviors among housewives in suburbs of Bandar-Abbas City, south of Iran: interventional design based on PRECEDE model

ABSTRACT Suburban areas suffer from unfavorable conditions as a result of poor health standards, low income, illness, and slight levels of education. One of the most important components in malaria elimination programs is health education. Bandar-Abbas is a malaria endemic city. Therefore, this study aimed to promote malaria preventive behaviors among housewives in suburbs of Bandar-Abbas City, Iran, through a PRECEDE model-based intervention program. This quasi-experimental study was carried out on 172 housewives under the coverage of four healthcare centers in Bandar-Abbas in 2016. The participants were randomly divided into two experimental and control groups, based on the inclusion criteria. The data collection tools included ademographic questionnaire, aresearcher-made questionnaire based on the educational phase of the PRECEDE model and achecklist for assessing malaria preventive behaviors. After the pre-test, the educational intervention was implemented on the intervention group at the first stage and the same questionnaire was administered as the post-test for both groups two months after the intervention. In this study, after implementing the intervention using the PRECEDE educational program, asignificant difference was found between the intervention and control groups in the mean scores for predisposing factors (knowledge and attitude) (P< 0.001), enabling factors (P< 0.001) and reinforcing factors (P< 0.001), which contributed to the improvement of preventive behaviors (P< 0.001). The PRECEDE model-based health education was effective in increasing knowledge and attitude, enabling and reinforcing factors, and promoting malaria preventive behaviors in the studied endemic areas.
Extracellular vesicles in bone and tooth: A state‐of‐art paradigm in skeletal regeneration

Bone and tooth, fundamental parts of the craniofacial skeleton, are anatomically and developmentally interconnected structures. Notably, pathological processes in these tissues underwent together and progressed in multilevels. Extracellular vesicles (EVs) are cell‐released small organelles and transfer proteins and genetic information into cells and tissues. Although EVs have been identified in bone and tooth, particularly EVs have been identified in the bone formation and resorption, the concrete roles of EVs in bone and tooth development and diseases remain elusive. As such, we review the recent progress of EVs in bone and tooth to highlight the novel findings of EVs in cellular communication, tissue homeostasis, and interventions. This will enhance our comprehension on the skeletal biology and shed new light on the modulation of skeletal disorders and the potential of genetic treatment.