Miracle-dz/UniFAR-FTUs huggingface dataset:
Overexpression of Orai1 and STIM1 Proteins Alters Regulation of Store-operated Ca2+ Entry by Endogenous Mediators*

Background: Store-operated Ca2+ entry (SOCE) is essential for cell function. Results: We discovered cross-talk between expression of molecules that determine SOCE and demonstrated that the role of endogenous mediators may be altered in overexpressed system. Conclusion: iPLA2β is an important regulator of endogenous SOCE, but its role can be obscured by Orai1 and STIM1 overexpression. Significance: Mediators of endogenous SOCE are important for Ca2+ homeostasis in health and disease. Orai1 and STIM1 have been identified as the main determinants of the store-operated Ca2+ entry (SOCE). Their specific roles in SOCE and their molecular interactions have been studied extensively following heterologous overexpression or molecular knockdown and extrapolated to the endogenous processes in naïve cells. Using molecular and imaging techniques, we found that variation of expression levels of Orai1 or STIM1 can significantly alter expression and role of some endogenous regulators of SOCE. Although functional inhibition of Ca2+-independent phospholipase A2 β (iPLA2β or PLA2g6A), or depletion of plasma membrane cholesterol caused a dramatic loss of endogenous SOCE in HEK293 cells, these effects were attenuated significantly when either Orai1 or STIM1 were overexpressed. Molecular knockdown of iPLA2β impaired SOCE in both control cells and cells overexpressing STIM1. We also discovered important cross-talk between expression of Orai1 and a specific plasma membrane variant of iPLA2β but not STIM1. These data confirm the role of iPLA2β as an essential mediator of endogenous SOCE and demonstrate that its physiological role can be obscured by Orai1 and STIM1 overexpression.
A Microbial Polysaccharide Reduces the Severity of Rheumatoid Arthritis by Influencing Th17 Differentiation and Proinflammatory Cytokines Production1

Rheumatoid arthritis (RA) is a chronic and debilitating autoimmune disease characterized by chronic joint inflammation with subsequent cartilage and bone destruction. RA is emerging as a model of IL-17-driven autoimmune inflammatory disease. IL-17 is a marker for Th17 cells, with its master regulator being the retinoic acid receptor-related orphan receptor (RORγt) regulated by STAT3 signaling. Glucuronoxylomannan (GXM), a polysaccharide representing the main component of the capsular material of the opportunistic yeast Cryptococcus neoformans, exhibits potent immunosuppressive properties both in vitro and in vivo. The present study investigates the effects of GXM treatment on the progression of collagen-induced arthritis. GXM suppressed clinical signs of collagen-induced arthritis and blocked joint erosion progression. This effect was mediated by down-regulation of key cytokines involved in the pathogenesis of RA such as TNF-α and IL-1β, and up-regulation of the inhibitory cytokine IL-10. Moreover, a reduction of IL-6 and TGF-β, which inhibit Th17 differentiation with consequent decreased IL-17 production at the local and systemic level, was observed. The effect of GXM on Th17 differentiation mirrored the reduction in STAT3 activation and inhibition of RORγt synthesis. Consequently, this work highlights the beneficial properties of an efficacious compound that could eventually be destined to the clinic.
Andropause: knowledge and awareness among primary care physicians in Victoria, BC, Canada

The causes, symptoms and treatment options for andropause have been well documented; however, not enough is known about the primary care physicians' (PCPs) knowledge in this therapeutic area. This study assesses the PCPs' awareness and knowledge of andropause in Victoria, British Columbia, Canada. Methods. Self-administered questionnaires were developed for family physicians and general practitioners. Each questionnaire included questions in three domains: 1) General knowledge, beliefs and exposure; 2) Knowledge of diagnostic and treatment options and; 3) General demographics. Results. A very high percentage of PCPs had heard of andropause (96.3%). Of the physicians who completed the survey, 92.6% agreed that men experience something similar to women's menopause when they age and 98.0% agreed that andropause is associated with an increased risk of osteoporosis. Almost all PCPs (91.5%) agreed that prostate cancer is a contraindication to treatment while around one-third (33.9%) agreed that breast cancer was a contraindication. Slightly more than half of physicians (57.4%) felt that they encountered obstacles to their investigation of andropause with the most prevalent complaint being a lack of access to education resources. There is a need for improved continuing medical education (CME) programmes in the Greater Victoria region to give PCPs the skills to diagnose and manage andropause with confidence.
High-Frequency Sensorineural Hearing Loss After Stapedectomy

Objective: To describe the pattern and duration of high frequency sensorineural hearing loss after stapedectomy. Study Design: Retrospective case series. Setting: Tertiary referral center. Patients: All patients who underwent stapedectomy by the senior author during the period between January 1, 1998, and October 1, 2005, with preoperative, 4- to 6-week postoperative, and at least 9-month postoperative audiograms were included. Fifty-three patients met the inclusion criteria, with surgeries performed on 61 ears. Intervention(s): Stapedectomy was performed using a CO2 laser. Main Outcome Measure(s): Mean preoperative and postoperative pure-tone bone thresholds, mean preoperative and postoperative pure-tone air thresholds, and hearing outcomes for 4,000 Hz bone conduction (BC) and 8,000 Hz air conduction (AC) based on the patient's age and interval after the operative procedure. Results: Mean BC thresholds at 4,000 Hz BC worsened by 6 dB at 4 to 6 weeks and improved by 3 dB by 9 months. There was an 8-dB average loss at 8,000 Hz AC at 4 to 6 weeks with a gain of 4 dB by 9 months. Patients older than 40 years were 4 times more likely to experience early loss at 4,000 Hz BC when preoperative thresholds were held constant. The late outcome for hearing loss was dependent more on the preoperative threshold than was the age of the patient. At 8,000 Hz AC, the preoperative hearing threshold was a predictor of early and late hearing loss at 8,000 Hz. Conclusion: High-frequency sensorineural hearing loss is initially seen after stapes surgery, and improvement does occur over time. When preoperative hearing threshold is held constant, patients older than 40 years are more likely to experience short-term hearing loss at high frequencies than patients younger than 40 years. Age was not a predictor of postoperative high-frequency hearing loss in the long term.
Should aggressive thoracic therapy be performed in patients with synchronous oligometastatic non-small cell lung cancer? A meta-analysis.

BACKGROUND We performed a meta-analysis to compare overall survival (OS) outcomes in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC) who underwent aggressive thoracic therapy (ATT) with those who did not. METHODS A systematic review of controlled trials of ATT on survival in synchronous oligometastatic NSCLC was conducted. Hazard ratio (HR) for the main endpoint OS was pooled using a fixed-effects model. Subgroup analysis was performed in patients with single organ metastases, or with different numbers of brain metastases, or with different stages of thoracic disease. Pooled survival curves of OS were constructed. RESULTS Seven eligible retrospective observational cohort studies were identified including 668 synchronous oligometastatic NSCLC patients, of whom 227 (34.0%) received ATT. For patients with synchronous oligometastatic NSCLC, ATT was associated with a significant improvement of OS (HR, 0.48; 95% CI, 0.39-0.60; P<0.00001). In subgroup analysis, the association with OS was similar or even strengthened, with a HR of 0.42 (95% CI, 0.31-0.56) in single organ metastases group, 0.49 (95% CI, 0.31-0.75) in solitary brain metastasis group, and 0.38 (95% CI, 0.20-0.73) in thoracic stage I-II group, respectively. The pooled cumulative survival rates for patients received ATT were 74.9% at 1 year, 52.1% at 2 years, 23.0% at 3 years, and 12.6% at 4 years. The corresponding pooled survival for patients who did not receive ATT were 32.3%, 13.7%, 3.7%, and 2.0%, respectively. CONCLUSIONS Survival benefit from ATT is common in synchronous oligometastatic patients. Selected patients with synchronous oligometastatic NSCLC could also achieve long-term survival with ATT.
Deep mutational scanning of an RRM domain of the Saccharomyces cerevisiae poly(A)-binding protein

The RNA recognition motif (RRM) is the most common eukaryotic RNA-binding domain, with differences in its amino acid sequence affecting binding specificity and affinity. This study applied a deep mutational scanning approach to score the functional activity of more than 100,000 variants of the RRM2 domain of the yeast poly(A)-binding protein, Pab1. The authors use these data to refine the current understanding of the Pab1 domain and of RRM domains in general.
Management of Facial Fractures in Children and Adolescents

The surgical management of facial fractures in children has evolved gradually. Children sustaining facial fractures have not benefited equally as their adult counterparts from the rapid refinements in the management of facial trauma. Only recently have the distinct advantages of accurate primary repair of facial fractures been applied to the rehabilitation of the injured child. The pattern of craniomaxillofacial fractures seen in children and adolescents varies with their evolving skeletal anatomy and socioenvironmental factors. A personal philosophy for the effective management of the craniomaxillofacial injuries that tend to occur in facially traumatized children and adolescents is reviewed.
An Emerging Postural Response: Is Control of the Hip Possible in the Newly Walking Child?

Previous researchers have proposed that because of their slow muscle-response latencies, 1- to 2-year-old children are unable to control hip-dominant postural responses when responding to balance threats (G. McCollum & T. Leen, 1989). To test that proposition, the authors exposed 41 children to backward support-surface translations and recorded muscle activations and movement kinematics. Children between 10 months and 10 years of age stood on a platform that was unexpectedly moved. Passive hip-dominant responses were observed among the least experienced walkers. In contrast, older children produced an active response, signified by higher levels of abdominal and quadriceps muscle activity and accompanied by larger hip flexor torques. Greater success in withstanding large magnitudes of perturbations were associated with actively generated hip responses.
Percutaneous biportal endoscopic decompression for lumbar spinal stenosis: a technical note and preliminary clinical results.

OBJECTIVE The use of conventional uniportal spinal endoscopic decompression surgery for lumbar spinal stenosis can be limited by technical difficulties and a restricted field of vision. The purpose of this study is to describe the technique for percutaneous biportal endoscopic decompression (PBED) for lumbar spinal stenosis and analysis of clinical postoperative results. METHODS The authors performed a unilateral laminotomy with bilateral foraminal decompression using a unilateral biportal endoscopic system in patients with single-level lumbar stenosis. The authors enrolled only patients who underwent follow-up for longer than 12 months after PBED. Fifty-eight patients were enrolled in this study. This approach was based on 2 portals: one portal was used for continuous irrigation and endoscopic viewing and the other portal was used to manipulate the instruments used in the decompression procedures. Clinical parameters such as the Oswestry Disability Index (ODI), Macnab criteria, and postoperative complications were analyzed. RESULTS Neural decompression was effectively performed in all enrolled patients. The mean ODI was significantly lower after PBED. Of 58 patients, 47 (81.0%) had a good or excellent result according to the Macnab criteria. Postoperative ODI and visual analog scale scores were significantly improved compared with preoperative values. CONCLUSIONS From a surgical point of view, percutaneous biportal endoscopy is very similar to microscopic spinal surgery, permitting good visualization of the contralateral sublaminar and medial foraminal areas. The authors suggest that the PBED, which is a minimally invasive procedure, is an alternative treatment option for degenerative lumbar stenosis.
Could Honey Have a Place in Colitis Therapy? Effects of Honey, Prednisolone, and Disulfiram on Inflammation, Nitric Oxide, and Free Radical Formation

Background/Aims: The purpose of this study was to investigate the potential therapeutic roles of honey, prednisolone and disulfiram in an experimental model of inflammatory bowel disease. Another aspect of the study was to find out whether these substances have any effect on nitric oxide (NO) and free radical production. Methods: After the induction of colitis with trinitrobenzene sulfonic acid in 64 male rats, physiological saline, honey, prednisolone and disulfiram enemas were applied to the rats once daily for 3 days (acute treatment groups) or 7 days (chronic treatment groups). Control groups received only saline enemas. Rats were killed on the 4th or 8th days and their colonic mucosal damage was quantitated using a scoring system. Acute and chronic inflammatory responses were determined by a mucosal injury score, histological examination and measurement of the myeloperoxidase (MPO) activity of tissues. The content of malonylaldehyde (MDA) and NO metabolites in colon homogenates was also measured to assess the effects of these substances on NO and free oxygen radical production. Results: Estimation of colonic damage by mucosal injury scoring was found to be strongly correlated with the histologic evaluation of colon specimens. On the other hand, mucosal injury scores were not correlated with MPO, MDA or NO values. There were significant differences between the MPO results of chronic-control and chronic-honey groups, as well as chronic-control and chronic-prednisolone groups (p = 0.03 and p = 0.0007). The acute honey, prednisolone, and disulfiram groups had significantly lower MDA results compared to the acute control group (p = 0.04, p = 0.02, and p = 0.04). In terms of NO, there was no significant difference between the treatment and control groups. NO was found to have a strong relationship with MDA (p = 0.03) and MPO values (p = 0.001). On the other hand, MPO results were not found to be correlated with MDA values (p > 0.05). Conclusions: MPO activity is not directly proportional to the severity of the inflammation, but it may only determine the amount of neutrophil in the tissues. Inflammatory cells are not the sole intensifying factor in colitis. Therefore, mucosal injury scores may not correlate well with MPO activities. In an inflammatory state NO and MPO levels have a strong relationship, since NO is released from the neutrophils. In an inflammatory model of colitis, intrarectal honey administration is as effective as prednisolone treatment. Honey may have some features in the treatment of colitis, but this issue requires further investigation. Honey, prednisolone and even disulfiram also have some value in preventing the formation of free radicals released from the inflamed tissues. Prednisolone may also have some possible benefits in the inhibition of NO production in colitis therapy.
Pest Control by the Introduction of a Conditional Lethal Trait on Multiple Loci: Potential, Limitations, and Optimal Strategies

Abstract Advances in genetics have made it feasible to genetically engineerinsect strains carrying a conditional lethal trait on multiple loci. Wemodel the release into a target pest population of insects carrying adominant and fully penetrant conditional lethal trait on 1–20 loci.Delaying the lethality for several generations after release allows thetrait to become widely spread in the target population before beingactivated. To determine effectiveness and optimal strategies for suchreleases, we vary release size, number of generations until theconditional lethality, nonconditional fitness cost resulting from geneinsertions, and fitness reduction associated with laboratory rearing.We show that conditional lethal releases are potentially orders ofmagnitude more effective than sterile male releases of equal size, andthat far smaller release sizes may be required for this approach thannecessary with sterile males. For example, a release of male insectscarrying a conditional lethal allele that is activated in theF4 generation on 10 loci reduces the target population to10−4 of no-release size if there are initially tworeleased males for every wild male. We show how the effectiveness ofconditional lethal releases decreases as the nonconditional fitnessreduction (i.e., fitness reduction before the trait becomes lethal)associated with the conditional lethal genes increases. For example, ifthere is a 5% nonconditional fitness cost per conditional lethalallele, then a 2:1 (released male:wild male) release with conditionallethal alleles that are activated in the F4 generationreduces the population to 2–5% (depending on the degree of densitydependence) of the no-release size. If there is a per-allele reductionin fitness, then as the number of loci is increased there is atrade-off between the fraction of offspring carrying at least oneconditional lethal allele and the fitness of the released insects. Wecalculate the optimal number of loci on which to insert the conditionallethal gene given various conditions. In addition, we show howlaboratory-rearing fitness costs, density-dependence, and all-maleversus male-female releases affect the efficiency of conditional lethalreleases.
Vector Field Smoothing for DOA Estimation of Coherent Underwater Acoustic Signals in Presence of a Reflecting Boundary

A new vector field smoothing algorithm for direction-of-arrival (DOA) estimation of multiple coherent, underwater acoustic signals is proposed based on the array with vector hydrophones, which is located at or near a reflecting boundary. The performance of the proposed algorithm is examined in two practical applications: hull-mounted and seabed array. The advantage of the vector field smoothing scheme is no reduction in the overall array's spatial aperture.
Additional patient with del(12)(q21.2q22): further evidence for a candidate region for cardio-facio-cutaneous syndrome?

Cardio-facio-cutaneous (CFC) syndrome is characterized by a distinct facial appearance, cardiac defects, ectodermal anomalies and developmental delay. Recently, we reported a 19-month-old girl with phenotypic manifestations consistent with the CFC syndrome who had an interstitial deletion of the long arm of chromosome 12, del(12)(q21.2q22), implicating a possible locus for CFC syndrome. Here, we report an additional patient with a cytogenetically identical interstitial deletion: 47,XYY,del(12)(q21.2q22). To further characterize this deletion we used microarray-based comparative genomic hybridization (array CGH). Array CGH confirmed both the deletion and the second Y chromosome. The deletion on chromosome 12q spanned at least 14 Mb as indicated by the positions on the genome sequence of the 4 BAC clones included in the deletion. While the proband did not have the classic features of CFC, he had some dysmorphic craniofacial characteristics, ectodermal anomalies and moderate developmental delay which were suggestive of CFC syndrome; however, this patient did not have classical CFC. The phenotypic differences between the two del(12)(q21.2q22) patients may be due to variability in the expression of the syndrome, or this deletion may present as a syndrome with overlapping features. Alternatively, the phenotypic differences may result from discordance at the molecular level, which may yield a critical minimal region of deletion for CFC. The region 12q21.2 --> q22 remains a possible candidate region for CFC syndrome. Additional characterization of these and other CFC patients may confirm and further refine this candidate region.
Factors Associated with Teachers’ Motivation and Commitment to Teach in Tanzania

This study examined the level of teachers’ motivation and commitment to the teaching profession in Tanzania. The results show that the majority of teachers were motivated to join and stay in the teaching profession due to intrinsic, rather than extrinsic, factors such as intellectual curiosity and feelings of belongingness to learning community. The results also show that the majority of teachers have very low level of commitment to the teaching profession. For example, just about a third of the teachers surveyed reported that they would choose teaching profession if they were to consider choosing it again. The level of commitment to the teaching profession is associated with the school ownership category, whether a school is privately or publicly owned, and the level teaching qualification.
[An outbreak of scarlet fever, impetigo and pharyngitis caused by the same Streptococcus pyogenes type T4M4 in a primary school].

UNLABELLED EPIDEMIC: Following the notification of an unusual number of scarlet fever cases within the same primary school, the epidemiological and clinical features of the outbreak were investigated. Questionnaire information about the cases was collected from parents and general practitioners per telephone. Throat specimens were taken, before and after treatment, for culturing and specific typing of streptococci was performed to determine transmission. Within a period of one month, 21 schoolchildren in a class of 29 pupils, with a mean age of 5 years, presented with symptoms caused by streptococcal infection (attack rate: 72%). Eight had scarlet fever, 5 suffered from impetigo and 8 had pharyngitis. A further 6 children, outside of this class, had complaints of scarlet fever, impetigo or pharyngitis. For 90% (26/29) of the schoolchildren a throat culture was established. Twelve positive cultures of the same strain of beta-haemolytic group A streptococcus, T4M4 exotoxin C gene positive, were found. The advice given was to treat all positive children for 3 days with azithromycin to prevent complications and further spreading of the disease. After two weeks only one child, that had not taken the antibiotics, still had a positive throat culture. No further cases or complications were reported. DISCUSSION The pattern of the outbreak was typical of a person-to-person transmission. This was confirmed by typing of the isolates. The results of this study demonstrate the importance of mandatory notification of infectious clusters by institutions, such as schools, as introduced in the new Dutch Infectious Disease Act. On the one hand, the notification gives the municipal health authority the opportunity to analyse source and transmission dynamics and on the other to prevent disease and complications.