Pediatric histiocytic neoplasms are hematopoietic disorders frequently driven by the BRAF-V600E mutation. Here we identified two BRAF gene fusions (novel MTAP-BRAF and MS4A6A-BRAF) in two aggressive histiocytic neoplasms. In contrast to previously described BRAF fusions, MTAP-BRAF and MS4A6A-BRAF do not respond to the paradox breaker RAF inhibitor (RAFi) PLX8394 due to stable fusion dimerization mediated by the N-terminal fusion partners. This highlights a significant and clinically relevant shift from the current dogma that BRAF-fusions respond similarly to BRAF-inhibitors. As an alternative, we show suppression of fusion-driven oncogenic growth with the pan-RAFi LY3009120 and MEK inhibition.
In this study, we propose to derive an accurate numerical procedure to solve the mathematical model which describes the electrical R-L circuit composed of resistors and inductors driven by a voltage of current source, which is the fractional-order model for the electrical RL-circuit. Our study depends on the spectral collocation method via the useful properties of the Chebyshev polynomials of the third-kind. Some theorems about the convergence analysis are given. The study concludes by comparing the resulting approximate solutions of the proposed model with the exact solution in the classical case. Illustrative graphical and numerical analysis of the derived results are also included in this study.
In this study, we introduce concepts of norms of elliptic complex matrices and derive the least squares solution, the pure imaginary least squares solution, and the pure real least squares solution with the least norm for the elliptic complex matrix equation AX=B by using the real representation of elliptic complex matrices. To prove the authenticity of our results and to distinguish them from existing ones, some illustrative examples are also given. Elliptic numbers are generalized form of complex and so real numbers. Thus, the obtained results extend, generalize and complement some known least squares solutions results from the literature.
Decomposition of forest litter plays a major role in nitrogen (N) dynamics in soil. But to which extent that forest litter affects soil N and how much soil N is derived from the new litter remains unknown. An in-situ soil column experiment with 14-month litter decomposition was conducted to examine the effect of litter retention on soil N dynamics in a typical forest of subtropical China in 2018. Litter removal in the soil column was used as a control treatment, while natural litter or identical amount of 15N labeled litter was added to soil columns as litter retention treatment. The results showed that litter removal caused a continuous decrease in concentration of soil soluble organic nitrogen (SON) in the first 5 months, and then SON began to accumulate and its concentration went up in spring showing obvious seasonal change. Litter retention accelerated the reduction of soil SON concentration in the first 2 months, while maintained a high concentration after that period. Soil NH4+-N derived from litter was nitrified rapidly, and newly formed NO3–N was quickly immobilized or lost. Only 1.8% of soil SON came from litter N and 98.2% from indigenous soil N under the decomposition of labeled litter. Litter provided supplementation N to form new soil SON continuously, however, only a small part of SON was relatively stable, and SON played the role of reserve and regulatory pool. Soil SON and TN were formed after long-term litter accumulation and decomposition.
Objectives: The objective of the present study was to investigate the effect of the Pulmonary Rehabilitation Program on work productivity, disease activity, functional status, quality of life, Respiratory Function Tests (RFTs), physical capacity,and depression in Ankylosing Spondylitis (AS) patients. Method: Twenty-five patients diagnosed with AS were included in the study. The disease severity was evaluated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), functional status was evaluated with Bath Ankylosing Spondylitis Functional Index (BASFI), and quality of life was evaluated with AS-Related Quality of Life scale (ASQOL). Physical capacity was evaluated with the 6-Minute Walking Test (6MWT), depression level was evaluated with Beck Depression Scale (BDS),and work productivity was evaluated with Spondyloartropathy Work Productivity and Activity Impairment (WPAI-SpA) Survey. RFT was evaluated with spirometry measurement. The patients were included in the Pulmonary Rehabilitation Program for 8 weeks. Results: A total of 30% of the patients who were included in the study were unemployed; 35% of them were on and below hunger limit; 25% were on and below poverty line; and 40% were on normal income line. No significant changes were detected in the RFTs after the exercise program in AS patients (p > 0.05), but significantly improvements were detected in the BASDAI, BASFI, WPAI, 6MWT, ASQOL and BDS scales (p <0.001). Conclusion: Pulmonary Rehabilitation Program was found to be an effective method of improving work productivity in AS patients. Also, the Pulmonary Rehabilitation Program has positive effects on disease activity, functional status, physical capacity, depression level, and quality of life.
The bean bug (Riptortus pedestris) causes great economic losses of soybeans by piercing and sucking pods and seeds. Although R. pedestris has become the focus of numerous studies associated with insect–microbe interactions, plant–insect interactions, and pesticide resistance, a lack of genomic resources has limited deeper insights. In this study, we report the first R. pedestris genome at the chromosomal level using PacBio, Illumina, and Hi-C technologies. The assembled genome was 1.193 Gb in size with a contig N50 of 13.97 Mb. More than 95.7% of the total genome bases were successfully anchored to 6 unique chromosomes, with the scaffold N50 reaching 181.34 Mb. Genome resequencing of male and female individuals and chromosomic staining demonstrated that the sex chromosome system of R. pedestris is XO, and the shortest chromosome is the X chromosome. In total, 21,562 protein-coding genes were predicted, 21,320 of which were validated as being expressed in different tissues or different developmental stages. Evolutionary analysis demonstrated that R. pedestris and Oncopeltus fasciatus formed a sister group and split ∼35 million years ago. Additionally, a 5.04 Mb complete genome of symbiotic Serratia marcescens Rip1 was assembled, and the virulence factors that account for successful colonization in the host midgut were identified. The high-quality R. pedestris genome provides a valuable resource for further research, as well as for the pest management of bug pests.
Abstract Background Lung ultrasound (LUS) has been used to diagnose neonatal respiratory diseases. However, few simple method has been reported to predict respiratory support needs(RSN). Our aim was to determine the diagnostic accuracy of a semiquantitative LUS assessment method predicting respiratory support need. Methods We conducted a prospective diagnostic accuracy study following the STARD (Standards for the Reporting of Diagnostic Accuracy Studies) guidelines at a tertiary level academic hospital between 2019 and 2020. After birth, infants were transferred to a monitoring room to determine NICU treatment need. 310 late preterm and term infants with respiratory symptoms enrolled. The LUS assessment was performed for each participant at one of the following times: 0.5 h, 1 h, 2 h, 4 h, and 6 h after birth. Reliability was tested by ROC analysis. Surfactant administration and other RSNs were based on the 2019 European guidelines as well as the infant’s clinical condition. Results 74 have RSN, and 236 were healthy according to a 3-day follow-up confirmation. Six LUS imaging patterns were found. Two “high-risk” patterns were highly correlated with RSN(area under the curve (AUC) = 0.95; 95% CI, 0.92-0.98, p<0.001). This accuracy is supported by the AUC of “low-risk” patterns (0.89, 95% CI, 0.85-0.93, p<0.001). The predictive value of LUS is greater than that of only using respiratory symptoms (e.g., respiratory rate) (AUC of LUS vs AUC of respiratory rate, p<0.01). Conclusions LUS is a useful tool to predict RSN and is more reliable than assessments based on respiratory symptoms alone.
In a recent paper, “Environmental DNA: What’s behind the term? Clarifying the terminology and recommendations for its future use in biomonitoring”, Pawlowski et al. argue that the term eDNA should be used to refer to the pool of DNA isolated from environmental samples, as opposed to only extra-organismal DNA from macro-organisms. We agree with this view. However, we are concerned that their proposed two-level terminology specifying sampling environment and targeted taxa is overly simplistic and might hinder rather than improve clear communication about environmental DNA and its use in biomonitoring. Not only is this terminology based on categories that are often difficult to assign and uninformative, but it ignores what is in our opinion the most important distinction within eDNA: the type of DNA (organismal or extra-organismal) from which ecological interpretations are derived.
This paper aims to solve the celebrated Fuzzy Fractional Differential Equations (FFDE) using an Artificial Neural Network (ANN) technique. Compared to the integer order differential equation, the proposed FFDE can better describe several real application problems of various physical systems. To accomplish the aforementioned aim, the error back propagation algorithm and a multi-layer feed forward neural architecture are utilized using the unsupervised learning in order to minimize the error function as well as the modification of the parameters such as weights and biases. By combining the initial conditions with the ANN, output provides an appropriate approximate solution of the proposed FFDE. Then, two illustrative examples are solved to confirm the applicability of the concept as well as to demonstrate both the precision and effectiveness of the developed method. By comparing with some traditional methods, the obtained results reveals a close match that confirms both accuracy and correctness of the proposed method.
Aims To evaluate the effect of severe chronic obstructive pulmonary disease (COPD) on drug metabolism by comparing the pharmacokinetics of patients with severe COPD with healthy volunteers and using the modified ‘Inje’ drug cocktail. Methods This was a single-centre pharmacokinetic study with 12 healthy participants and 7 participants with GOLD D COPD. Midazolam 1 mg, dextromethorphan 30 mg, losartan 25 mg, omeprazole 20 mg, caffeine 130 mg, and paracetamol 1000 mg were simultaneously administered and intensive pharmacokinetic sampling was conducted over 8 hours. Drug metabolism by CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP1A2, UGT1A6 and UGT1A9 in participants with COPD were compared with phenotypes in healthy controls. Results The oral clearance (95% CI) in participants with COPD relative to controls was: midazolam 63% (60-67%), dextromethorphan 72% (40-103%), losartan 53% (52-55%), omeprazole 35% (31-39%), caffeine 52% (50-53%), and paracetamol 73% (72-74%). There was a five-fold increase in AUC for omeprazole and approximately two-fold increases for caffeine, losartan, dextromethorphan, and midazolam. The AUC of paracetamol, which is mostly glucuronidated, was increased by about 60%. Conclusion Severe COPD is associated with a clinically significant reduction in drug clearance. This may be greater for cytochrome P450 substrates than for glucuronidated drugs. This supports reduced starting doses when prescribing for patients with severe COPD.
Aim In this study, we aimed to investigate the effectiveness of ozone therapy, which is one of the integrative medicine applications that has been used safely for many years, on the prevalence of mortality in patients receiving COVID-19 treatment. Methods This was a prospective, controlled study conducted on patients with COVID-19 who were hospitalized in Health Sciences University, Haydarpasa Numune Training and Research Hospital. In this study, 55 patients were included. The patients were divided into two groups as the ozone group and the control group. Ozone therapy (major autohemotherapy) was applied to 37 patients who were being treated with the appropriate COVID-19 treatment protocol determined by the infectious diseases committee of our hospital. The ozone treatment protocol consisted of seven sessions (1 session/day) of intravenous ozone administration, applied in a volume of 100 mL and a concentration of 30 μg/mL. Only the conventional COVID-19 treatment protocol was applied to 18 patients in the control group. Clinical follow-up was performed until the discharge of the patients from the hospital with successful treatment or until the mortality occurred. Factors affecting mortality were analyzed using univariate regression analysis. Results Intensive care unit (ICU) hospitalization was required in six of 37 patients who were treated with ozone (16.2%), while four of 18 patients in the control group required ICU treatment (22.2%) (p = 0.713). When the mortality rates between the two groups were compared, mortality was lower in the ozone group (p = 0.032). As a result of univariate logistic regression analysis performed to determine the factors affecting mortality, treatment without ozone therapy was determined as a risk factor for mortality (OR:0.149, 95%CI 0.026-0.863, p=0.034). Conclusion In this study, we demonstrated that administration of ozone therapy along with the conventional medical treatment in patients hospitalized for COVID-19 could reduce mortality.
Fetal lung fluid: Not the same as amniotic fluidAuthor: Hemananda Muniraman MBBS, FAAP, FRCPCHAffiliations:Creighton University School of Medicine, Phoenix Campus, Arizona, USCorresponding Author: Hemananda Muniraman, MBBS, FAAP, FRCPCHAssistant Professor of Pediatrics Affiliate, Creighton University School of MedicinePhoenix Campus, 350 W Thomas Rd, Phoenix, AZ, US 85013Email; [email protected], Phone: +16022564628 Fax: +16026276325Conflict of Interest Disclosure: I have no conflicts of interest relevant to this article to disclose. Funding/Support.No funding to be reportedKey words: Extreme preterm, neonates, pneumatocele, fetal lung fluidDear Dr MurphyEditor in chief, Pediatric PulmonologyI read with interest the recently published article “Pulmonary pneumatoceles in neonates” by Dr Rocha.  It is a well written comprehensive review of pulmonary pneumatoceles in neonates and an important resource for the clinicians in decision making, that I found to be very insightful whilst recently managing an extreme preterm with a large pneumatocele.However, I wanted to bring attention to a statement in the introduction where the author states that the “preterm infants’ lungs are filled with amniotic fluid”. This is not accurate and appears to be a common misconception, particularly among medical students and junior residents despite recognition of fetal lung fluid as being a separate entity from the amniotic fluid as originally described in 1948 by Jost and Policard.  I believe this is an important knowledge gap that needs to be addressed. Understanding of metabolism and role of fetal lung fluid in lung development and postnatal transition is essential to clinicians involved in the care of newborns and infants.Though a comprehensive review of fetal lung fluid is beyond the scope of this letter, I provide a brief basic overview of fetal lung fluid with references for more comprehensive reading.Fetal lung fluid is a chloride rich acidic fluid produced with in the fetal lungs by secretion of chloride across the distal lung epithelial cells and is a major determinant for fetal lung growth and development. The fluid lung volume is maintained by transglottic pressure gradient with periodic egress of excess fluid during fetal breathing. Decreased lung fluid volume is associated with pulmonary hypoplasia and conversely, upper airway lesions obstructing the egress of lung fluid leads to increase in fetal lung fluid and volume, a principle used in fetal interventions such as endoluminal tracheal occlusion to enhance pulmonary growth in conditions namely congenital diaphragmatic hernia. [2,3,4]As important the fetal lung fluid is for lung development, clearance of lung fluid is crucial for normal postnatal transition and establishment of air filled lungs for effective gas exchange. Clearance of lung fluid is a complex and coordinated process that starts before the process of birth itself. The rate of lung fluid secretion diminishes before labor at term gestation. Catecholamines namely epinephrine released during labor upregulates the epithelial sodium channels (ENaC) promoting influx of sodium and fluid from lumen into pulmonary interstitial space thereby reversing the direction of fluid movement in the perinatal period. Lung fluid is decreased to about 35% following active labor and birth which are further cleared with neonatal cry and breathing and inflow of air after birth. The fluid from the interstitial space is cleared over the next few hours via pulmonary circulation and lymphatic drainage. However this process is impaired in infants delivered by elective cesarean sections leading to increased retained lung fluid after birth and resulting in transient respiratory distress and tachypnea of newborn (TTN). In preterm infants, catecholamine induced fluid reabsorption via ENaC is limited and may contribute to respiratory distress after birth. Prenatal maternal steroids and triiodothyronine administration is known to induce expression of messenger RNA for ENaC subunits in the fetal lungs and may facilitate lung fluid clearance. [2,4]Lastly, amniotic fluid aspiration into fetal lungs, with and without meconium contamination, has been reported to be the cause of respiratory distress with case reports of massive amniotic fluid aspiration noted on postmortem histological examination of newborn lungs. References:Rocha G. Pulmonary pneumatoceles in neonates. Pediatr Pulmonol. 2020 Jul 21. doi: 10.1002/ppul.24969. Epub ahead of print. PMID: 32691976.Katz C, Bentur L, Elias N. Clinical implication of lung fluid balance in the perinatal period. J Perinatol. 2011 Apr;31(4):230-5. doi: 10.1038/jp.2010.134. PMID: 21448181.Hooper SB, Harding R. Fetal lung liquid: a major determinant of the growth and functional development of the fetal lung. Clin Exp Pharmacol Physiol. 1995 Apr;22(4):235-47. doi: 10.1111/j.1440-1681.1995.tb01988.x. PMID: 7671435Kallapur S, Jobe A; Fetal Lung fluid. Richard J. Martin, Avroy A. Fanaroff, Michele C. Walsh. Fanaroff And Martin’s Neonatal-Perinatal Medicine : Diseases of the Fetus and Infant, 10th edition. Philadelphia, PA :Elsevier/Saunders, 2015Lavezzi AM, Poloniato A, Rovelli R, Lorioli L, Iasi GA, Pusiol T et al. Massive Amniotic Fluid Aspiration in a Case of Sudden Neonatal Death With Severe Hypoplasia of the Retrotrapezoid/Parafacial Respiratory Group. Front Pediatr. 2019 Apr 4;7:116. doi: 10.3389/fped.2019.00116. PMID: 31019904
Pulmonary hypertension represents an increasingly important group of pediatric patients which commonly come to the attention, if not the primary care of pediatric pulmonologists around the world. There have been major advances in diagnosis and therapy over the past 25 years. To address potential gaps in knowledge, the authors were invited by the Editor of Pediatric Pulmonology to organize a series of manuscripts in a special supplement of the journal. Our authors include pulmonologists, pharmacists, intensivists, mid-level practitioners, neonatologists and cardiologists. We believe that this issue will be of great interest to most of the readership community that the Journal addresses.
Several species of soil free-living saprotrophs can sometimes establish biotrophic symbiosis with plants, but the basic biology of this association remains largely unknown. Here, we investigate the symbiotic interaction between a common soil saprotroph, Clitopilus hobsonii (Agaricomycetes), and the American sweetgum (Liquidambar styraciflua). Notably, the colonized root cortical cells contain numerous microsclerotia-like structures. Fungal colonization led to increased plant growth and facilitated potassium uptake, particularly under potassium limitation (0.05 mM K+). The expression of plant genes related to potassium uptake is not altered during symbiosis, whereas the transcripts of three fungal genes encoding ACU, HAK, and SKC involved in K+ nutrition is found in colonized roots. We confirmed the K+ influx activities by expressing the ChACU and ChSKC genes into a yeast K+-uptake-defective mutant. Upregulation of the ChACU under 0.05 mM K+ and no K+ conditions was demonstrated in planta and in vitro compared to normal condition (5 mM K+). In addition, colonized plants displayed a larger accumulation of soluble sugars under 0.05 mM K+. The present study highlights that potassium limitation promotes this novel tree-fungus symbiosis mainly through a reciprocal transfer of additional carbon and potassium to both partners, and the role of dual soil saprotroph/symbiotroph in tree nutrition.
Patients with aortic dissection during pregnancy and postpartum period exhibit high mortality. At present, a complete overview of aortic dissection during pregnancy and postpartum period is lacking. This systematic review includes 80 reports published from 2000-2020, comprising a total study population of 103 patients with aortic dissection. It was suggested that Stanford Type A aortic dissection is more likely to occur in the third trimester, while Stanford Type B is more likely to occur within 12 weeks postpartum. The most common risk factor was connective tissue disease, with no other known risk factors. Mode of delivery has no significant effect on the type of postpartum aortic dissection. Reduced maternal and fetal mortality was observed when patients with Stanford Type A aortic dissection occurring after 28 gestational weeks underwent aortic replacement after cesarean section. Patients with Stanford Type B aortic dissection were treated mainly with medication and/or endovascular repair. Contemporary management of patients during pregnancy and within 12 weeks postpartum requires multidisciplinary cooperation and includes serial, non-invasive imaging, biomarker testing, and genetic risk profiling for aortopathy. Early diagnosis and accurate treatment are essential to reduce maternal and fetal mortality.
Objective: To assess the impact of surgeon experience on the outcomes of degenerative mitral valve disease. Methods: We reviewed all patients who had surgery for degenerative mitral valve disease between 2011-2016. Experienced surgeon was defined as performing 25 mitral valve operations/year. Patient characteristics and outcomes were compared. Multivariable analysis was performed to identify factors associated with MR recurrence. Survival analysis for mortality was done using Kaplan Meier curve and Cox proportional Hazard method. Results: There were 575 patients treated by 9 surgeons for severe mitral regurgitation caused by degenerative mitral valve disease between 2011-2016. Three experienced surgeons performed 77.2% of the operations. Patients treated by less experienced surgeons had worse comorbidity profile and were more likely to have an urgent or emergent operation (P=0.001). Experienced surgeons were more likely to attempt repair (P=0.024), to succeed in repair (94.7% vs 87%, P=0.001), had shorter cross-clamp times (P=0.001), and achieved higher repair rate (81.3% vs 69.7%, P=0.005). Experienced surgeons were more likely to use neochordae (P=0.001) and less likely to use chordae transfer (P=0.001). Surgeon experience was not associated with recurrence (moderate or higher MR) within the first two years after surgery but was an independent risk factor for mortality (HR= 2.64, P=0.002). Conclusions: Techniques of degenerative mitral valve surgery differ with surgeon experience, with higher rates of repair and better outcomes associated with more experienced surgeons.
Background: The purpose of this study was to investigate the incidence, predictors, and long-term impact of gastrointestinal (GI) complications following adult cardiac surgery. Methods: Index Society of Thoracic Surgeons (STS) adult cardiac operations performed between January 2010 and February 2018 at a single institution were included. Patients were stratified by the occurrence of postoperative GI complications. Outcomes included early and late survival as well as other associated major postoperative complications. A sub-analysis of propensity score matched patients was also performed. Results: 10,285 patients were included, and the overall rate of GI complications was 2.4% (n=246). Predictors of GI complications included dialysis dependency, intra-aortic balloon pump, congestive heart failure, chronic obstructive pulmonary disease, and longer aortic cross-clamp times. Thirty-day (2.6% vs 24.8%), one- (6.3% vs 41.9%), and three-year (11.1% vs 48.4%) mortality were substantially higher in patients who experienced GI complications (all P<0.001). GI complication was associated with a three-fold increased hazard for mortality (HR 3.1, 95% CI 2.6-3.7) after risk adjustment, and there was an association between the occurrence of GI complications and increased rates of renal failure (39.4% vs 2.5%), new dialysis dependency (31.3% vs 1.5%), multisystem organ failure (21.5% vs 1.0%), and deep sternal wound infections (2.6% vs 0.2%)(all P<0.001). These results persisted in propensity-matched analysis. Conclusions: GI complications are infrequent but have a profound impact on early and late survival, and often occur in association with other major complications. Risk factor modification, heightened awareness, and early detection and management of GI complications appears warranted.