Doxorubicin (DOX) is a highly useful antineoplastic in the treatment of different types of cancer; however, its use is limited due to its wide variability between patients in their susceptibility to the cardiotoxic effects of anthracyclines. Purpose: The aim of this study was to determine the effect of single nucleotide variants (SNV) and the nutritional status on the population pharmacokinetics of DOX, and their repercussions on cardiotoxicity in pediatric patients with leukemia. Patients and methods: Seventy pediatric patients treated with DOX were studied, in whom 189 biological samples (1 to 3 samples per patient) were obtained at different random times, for 20 hours. Results: Body mass index, age ≤ 7 years and female sex were associated with a decrease in DOX clearance. Low height was associated with an increase in pharmacokinetics parameters of DOX. The Wild type (WT) genotype of ABCC1 rs3743527 variant was associated with an increase in clearance (CL), and the homozygous variant (HV) genotype of NCF4 rs1883112 SNV was associated with a decrease in peripheral compartment (V2) of the peripheral compartment. Conclusion: The SNV of the ABCC1 and NCF4 genes influence the increase and decrease in DOX CL, in addition, characteristics such as sex and height were associated with the decrease and increase in DOX CL respectively. The pharmacokinetic parameters show an influence on the development of cardiotoxicity by DOX. The decrease in CL and V2 were associated with systolic disfunction. The decrease in the intercompartmental clearance (Q) and in the volume distribution (V2) were associated with diastolic disfunction. In clinical practice, these results may contribute to the effective and safe use of DOX in pediatric cancer patients.

Pediatric GIST (gastrointestinal stromal tumors) are mostly KIT/ PDGFRA-WT and harbor mutations in SDH (succinate dehydrogenase), making them TKI (tyrosine kinase inhibitor) resistant due to the absence of gain-of-function tyrosine kinase mutations. Due to rarity of GIST in children, there have been few clinical trials available for patients with advanced disease, resulting in limited treatment options and a lack of pediatric-specific consensus guidelines. Here, we report the case of a patient with progressive, metastatic SDHB-mutant GIST that displayed a significant clinical response with a combination of Olaparib and TMZ (temozolomide).

The sulfur cycle is one of the geochemical element cycles in which microorganisms play a key driving role. The microbial function of soil S cycling in response to desert degradation, however, remains largely unknown. We used metagenomics to analyze the characteristics of microbial communities and their functional genes involved in the S cycles under natural water gradients with three typical halophytes shrubs in the Ebinur Lake Basin Desert, China. Our results showed that the rhizosphere effect, water gradient, and halophyte type played a major role in shaping the S cycle. On the whole, in the rhizosphere type and low water environment, the functional genes involved in the S cycle had high abundance, and the SOX system in Alhagi sparsifolia had a high expression level. In the S cycle network structure, as the soil water content decreased, the complexity in S gene networks increased, showing the characteristics of clustering and high connectivity. Indicates the strengthening mode in microbial interactions with the water content. Interestingly, the negative correlation of the network changed with the water content, and there was more competition among communities under the low water gradient and more cooperation under the high water gradient. Through the correlation between environmental factors and the network, nitrate (NO 3 −) and soil available S (AS) constrained most S gene ecology networks. The key species involved in the S cycle were halophilic microorganisms. These results can enhance the understanding of soil S biogeochemical processes and contribute to the mitigation of desertification by improving soil conservation.

Understanding how evolutionary pressures relating to climate changes have shaped the genetic background of present day domestic animals is a fundamental pursuit in biology. Here, we generated whole genome sequence data from native goat populations in Iraq and Pakistan countries. Together with published data from worldwide modern, historical remains and wild caprid species (including ibex like species, bezoar and markhor goats) we explore genetic population structure, ancestry components and signatures of natural positive selection of native goat populations in Southwest Asia (SWA) region. Our results revealed that the genetic structure of SWA goats was deeply influenced by the gene flow from eastern Mediterranean area during the Chalcolithic period, which may reflect the adaptation to the gradual warming and aridity in this region. Furthermore, a comparative genomic analysis revealed adaptive introgression of KITLG locus from the Nubian ibex (Capra nubiana) into African and SWA goats. The frequency of the selected allele at this locus was found significantly higher among the goat populations located close to the north-east of Africa. The Nubian ibex is a wild relative of the domestic goat that is well adapted to the arid mountains of north Africa and the Middle East. These results provide new insights into the genetic composition and history of goat populations in SWA region.

Rydberg-atom electrometers have the remarkable advantages of self-calibration and high sensitivity. Based on the classical electromagnetic theory, a localized electric field enhancement structure of a hybrid rectangular resonator is proposed to improve the sensitivity of quantum microwave measurement. It should be noted that the prototype of the hybrid rectangular resonator is fabricated and measured at 9.925 GHz. The results of full-wave simulations show that the uniform and high electric field enhancement in the TE101 fundamental mode is realized. The transient process of resonance is simultaneously simulated, and the time to settle steady state is given as about 104 ns. As indicated through experimental results that the structure can reach 24 dB (enhancement factor of 15.8). As a result, the method proposed in this study, based on atomic measurement capabilities, enables us to improve the measurement sensitivity further and promotes the practical development of quantum microwave measurement technology.

Affective video content analysis is an active topic in the field of affective computing. In general, affective video content can be depicted by feature vectors of multiple modalities, so it is important to effectively fuse information. In this work, a novel framework is designed to fuse information from multiple stages in a unified manner. In particular, a unified fusion layer is devised to combine output tensors from multiple stages of the proposed neural network. With the unified fusion layer, a bidirectional residual recurrent fusion block is devised to model the information of each modality. Moreover, the proposed method achieves state-of-the-art performances on two challenging datasets, i.e., the accuracy value on the VideoEmotion dataset is 55.8%, and the MSE values on the two domains of EIMT16 are 0.464 and 0.176 respectively. The code of UMFN is available at: https://github.com/yunyi9/UMFN.

A document by Sree Krishna Das . Click on the document to view its contents.

Objective: This systematic review aimed to systematize different designs of exercise-based pulmonary rehabilitation (PR) for children with asthma and explore which designs are optimal. Methods: PubMed, EMBASE, Cochrane Library, Web of Science Core Collection and MEDLINE were searched up until April 01, 2021, which was conducted for any relevant randomized controlled trials (RCTs) of exercise-based PR in childhood asthma. Language is limited to English. Network meta-analyses and standard meta-analyses were performed using STATA (version 16.0), quality analyses were performed using RevMan (version 5.3). Results: A total of 24 RCTs involving 1031 patients were included. 14 studies were endurance training, which was the most commonly used form of exercise, and 7 studies rehabilitation sites were conducted in hospitals. A network meta-analysis showed that compared with other forms of exercise, interval training significantly improved the PAQLQ (Pediatric Asthma Quality of Life Questionnaire), including activity scores [MD=3.02, 95% CI (1.74,4.30)], symptom scores [MD=2.68, 95% CI (2.04,3.32)], emotional scores [MD=2.47, 95% CI (0.91,4.03)], and total scores [MD=2.68, 95% CI (1.79,3.57)]. Interval training [MD=188.97, 95% CI (-59.27, 437.21)] also had a more significant effect on the 6MWT (6-minute walk test). No adverse events were found in this study. Exercise training had no significant effect on FEV 1(the forced expiratory volume at 1s to predicted value ratio) [WMD=0.59, 95% CI (-2.00, 3.19)], however, the combined of endurance training and respiratory training was found to significantly improve both FVC (the forced vital capacity to predicted value ratio) [MD=5.37, 95% CI (0.07,10.67)] and FEF25-75% (the forced expiratory flow between 25% and 75% of vital capacity ratio) [WMD=11.31, 95% CI (2.13, 20.48)]. Conclusions: Exercise-based PR is a safe and effective for childhood asthma. Interval training may be a core component of improving quality of life and exercise capacity in childhood asthma, the combination of respiratory training and endurance training has significant effects on lung function.This result should be viewed with caution, and high-quality RCTs are still needed to confirm its clinical efficacy,

Background: Observational studies suggest that asthma/wheezing improve after adenotonsillectomy (AT). However, there is a paucity of RCT specifically studying the effects of AT in asthma/wheezing. Therefore, we conducted a post-hoc analysis of the Childhood Adenotonsillectomy Trial, the largest RCT of AT in children with obstructive sleep apnea (OSA) to test the hypothesis that AT would result in fewer wheezing episodes. Methods: In the CHAT study, 464 children with OSA, aged 5 to 9 years, were randomized to early AT (n=226) or watchful waiting with supportive care (WWSC) (n= 227). For this post-hoc analysis children were categorized as having “any wheezing” vs. “no wheezing” at baseline and at 7 months of follow-up. A multivariate analysis was conducted to evaluate the association between “any wheezing” at follow-up and treatment group after controlling for several potential confounders. Results: Children in the “any wheezing” group were predominantly black, had more allergic rhinitis, eczema, second-hand smoke exposure, more siblings and siblings with asthma, lower maternal education and family income than those in the “no wheezing group”. At baseline, wheezing characteristics were similar between AT and WWSC arms. At follow-up (at 7 months of the intervention) those in the AT arm had significatively less wheezing than those in the WWSC (22.4% vs. 43.8%, p=0.00001). However, the multivariate analysis of “any wheezing” vs. “no wheezing” at follow-up showed that the treatment arm was not associated with wheezing. Conclusion: This study demonstrated that AT has not effect on wheezing at 7 months of follow-up.

Through wind tunnel experiments, we measured the structure of surface drifting sand flux and sand transport rate on a bed surface that contained widely but uniformly spaced and non-erodible ridges. We found that under the condition of no ridges, the sand transport rate within the height of 0~70 cm on the bed surface decreases in a power function law with the increase of height, increases with the increase of friction velocity, and the proportion of sand transport rate at different high layers increases with the increase of height. The variation of sand transport rate with height can be divided into two cases for all the ridge heights and spacings: one shows that sand transport rate decreases exponentially with height, while the other shows that sand transport rate increases with height under a certain height, and above the certain height decreases exponentially with the increase of height, known as “elephant nose” effect which seems similar to the structure of drifting sand flux in Gobi desert. For all the ridge heights and spacings, the total sand transport rate in the height of 0~70 cm increases with the increase of friction velocity in a power function law, and increases with the increase of ridge spacing. When the friction velocity and ridge spacing are both large, the total sand transport rate of some ridge structures are larger than that with no ridges. Our results will contribute to the study on recognize the process and mechanism of soil wind erosion in ridge farmland.

Aims: The aim of this study was to evaluate the safety/tolerability, and pharmacokinetics (PKs) of rhEGF eyedrops after administration of a single and multiple doses in healthy subjects. Methods: A phase 1, randomized, double-blind, placebo-controlled, and single ascending dose (SAD) and multiple ascending dose (MAD) study were conducted in 3 dose groups (10, 50, and 100 μg/mL). The subjects randomly received rhEGF eyedrops or their placebo in a 3:1 ratio. Serial blood and tear samples for PK analysis were collected up to 36 h and 180 h post-dose in SAD and MAD study, respectively. In addition, the serum and tear EGF concentrations were measured. Immunogenicity evaluations were conducted using serum anti-EGF antibody level. Results: A total of 50 subjects were enrolled and 48 subjects completed the study. Adverse drug reactions were mild and transient. There were no serious adverse events in this study. The tear EGF concentrations rapidly increased and returned to baseline after 4 hours without serum EGF level change after the administration of rhEGF eyedrops. Conclusion: rhEGF eyedrops were safe and well-tolerated in healthy subjects in a dose range of 10-100 μg/mL, which indicated it was suitable for further studies for corneal injury patients.

Patients presenting with Class III malocclusion often present significant challenges for the orthodontist and restorative clinician. The characteristic anterior crossbite is commonly associated with a maxillo-mandibular skeletal base discrepancy leading to both functional and esthetic issues. Three potential incisal tooth positions are discussed using clinical examples including implants.

Patients with chronic myelogenous leukemia (CML) harboring the T315I mutation who progress to blast phase CML while on ponatinib may be successfully treated with asciminib monotherapy following induction therapy with cytotoxic chemotherapy.

The metacommunity framework has been rarely adopted to investigate the underlying ecological mechanisms shaping microbial communities. With the aid of advanced molecular techniques, we investigated sediment communities of Fungi, Bacteria and Archaea in four Italian show caves aiming to disentangle the effects induced by tourists on species richness and composition from environmental filtering and dispersal driven mechanisms. We modelled community changes against human disturbance ---measured as the distance from the tourist path---demonstrating that the presence of visitors in caves decreases fungal species richness and causes species replacement in Bacteria and Archaea. Environmental filtering affects species richness and composition of Fungi and species richness of Archaea, while a minor role was played by dispersal, influencing only species richness in Fungi. We provide new perspectives on the dynamics of microbial communities under human disturbance suggesting that a proper understanding of the underlying selective mechanisms requires a comprehensive and multi-taxonomic approach.

81-year-old man with a history of Bio-Bentall surgery presented to the emergency department with fever, chills and back pain. Initial physical examination was inconclusive apart from sudden onset of delirium, and investigation showed elevated WBCs, anemia, and neutrophilia. Further studies revealed gram-positive cocci on the initial blood culture, which was then confirmed to be MSSA bacteremia. Subsequently, a TEE showed a peri-aortic abscess, Moderate AR and severe AS with no evidence of endocarditis. Antibiotics were started and urgent abscess drainage was planned. In a hybrid operative setting, a multidisciplinary team of cardiology, and cardiac surgery managed the periaortic graft abscess drainage through a median sternotomy and TAVR. Post-operatively, the complications included bradycardia, and RHF. Six-week course of IV Rifampin, Probenecid and Cefazolin was initiated, and patient was to remain on lifelong Cefadroxil.

Caseous liquefaction necrosis of mitral annular calcifications are rare. Rupture of its capsule may lead to systemic embolization. Surgical management entails Incision and Drainage with either mitral valve repair or replacement.

A document by Dr. Muhammad Shehryar. Click on the document to view its contents.

Background: Urogenital changes associated with menopause are now classified as genitourinary syndrome of menopause (GSM) which includes symptoms of urgency, frequency, dysuria, and recurrent urinary tract infections (UTIs) for which the recommended, treatment is estrogen. However, the association between menopause and urinary symptoms and the efficacy of hormone therapy (HT) for these symptoms is uncertain. Objectives: Our objectives were (1) to define the relationship between menopause and urinary symptoms including dysuria, urgency, frequency, recurrent UTIs, and urge and stress incontinence, and 2) to systematically review the effects of HT for urinary symptoms in peri and post-menopausal women. Search strategy: PubMed, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched until April 2022 Selection criteria: RCTs of peri or postmenopausal women with urinary symptoms including dysuria, frequent UTI, urgency, frequency, and incontinence, in English were included. Data collection and analysis: Two authors reviewed each paper with discrepancies resolved through whole group consensus. Data extracted included: publication date, country, setting, subject number, follow-up, duration, age, race/ethnicity, study design, inclusion criteria, and main findings. Main results: There is insufficient evidence to confirm that menopause is associated with urinary symptoms. The effect of HT on urinary symptoms depends on type. Systemic HT may cause urinary incontinence or worsen existing urinary symptoms. Vaginal estrogen improves dysuria, frequency, urge and stress incontinence, and recurrent UTI in postmenopausal women. Conclusions: Menopause has not been shown to cause urinary symptoms. Vaginal estrogen improves urinary symptoms and decreases the risk of recurrent UTI in postmenopausal women.

Determination of the critical attack angle at which dynamic stall occurs has been a focus of research over the last few decades. This angle is usually determined by solving the Navier-Stokes equations, which includes viscosity, pressure, gravity, and acceleration terms. However, this article predicts the critical attack angle using Euler equations that do not contain viscous terms. The key contribution is the use of the Euler equations to capture the vortices and predict stall dynamics. The Euler equations are integrated and the resulting equations are discretized by the finite volume method. A first-order upwind-based method is used to calculate the convective fluxes at the cell boundaries in the finite volume approach. A NACA 0012 airfoil is chosen for this study at various attack angles with a Mach number of 0.3. Based on the justification of Crocco's theorem, the Euler equations successfully act as Navier-Stokes equations. The vortex patterns are found to behave independently of the artificial dissipation. All the vortices are successfully predicted using the inviscid governing equations. The obtained numerical results are validated by the existing experimental and numerical data.

Relapsed or refractive pediatric B-Acute Lymphoblastic Leukemia (B-ALL) patients have high rates of toxicities and relapse, and novel therapy is needed. We present a case of a 5-year-old male with high-risk B-ALL that was refractive to several re-induction regimens. He was put into MRD-negative remission after re-induction with chemotherapy plus overlapping rituximab, inotuzumab ozogamicin and blinatumomab, termed Mini-Hyper-CVD plus CRIB. This was well tolerated, and he received his transplant and engrafted with no significant infections, toxicities, or sinusoidal obstruction syndrome. This is the first reported use in pediatrics of a condensed sequential immunotherapy/chemotherapy regimen in a pediatric leukemia patient.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common leukemia in the pediatric population, caused by a malignant clonal proliferation of B lymphoid progenitor cells. Identifying new molecular markers related to B-cell development is helpful for investing the pathogenesis of B-ALL, and is potentially important for clinical prognosis. We found that B cells showed the highest expression of glutaminyl-tRNA amidotransferase subunit QRSL1 (QRSL1) compared with other cells during the differentiation and development of hematopoietic stem cells and the expression of QRSL1 also gradually increases with the development of human fetal B-cell. Moreover, QRSL1 expression was higher in the tissues and cell lines extracted from patients with B-ALL than in corresponding control tissues. In the TARGET cohort, EFS and OS decreased in B-ALL with high expression of QRSL1, suggesting that QRSL1 was an independent prognostic factor. And high QRSL1 expression is associated with more bone marrow sites of relapse and TCF3-PBX1 gene fusions. Then analyzing the gene expression of the TCF3-PBX1 gene fusion subgroup, the significantly different gene expression between the QRSL1 low group and QRSL1 high group exhibited enrichment in cell development, suggesting that QRSL1 may participate in leukemic cell development in childhood B-ALL. Therefore, QRSL1 may be a molecule related to B cell development and is associated with molecular subtypes of B-ALL. The high expression of QRSL1 is associated with poor prognosis in patients with B-ALL, showing its potential as a prognostic marker of B-ALL leukemia.

Mesothelioma is a rare and aggressive tumor originating from the serosal lining of the pleural, peritoneal and pericardial cavities. There are very few cases diagnosed with malignant peritoneal mesothelioma reported in childhood. Thanks to the developments in the field of immunotherapy, the prognosis of the disease has improved with the addition of the immune check point inhibitor, an anti-programmed death-1 monoclonal antibody, nivolumab to the treatment of MPM. In the treatment of our case who was diagnosed with diffuse malignant peritoneal mesothelioma at a very early age; cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, platinum and pemetrexed combination chemotherapy and nivolumab were used. Our patient, who has been on nivolumab therapy for 14 months and has been followed up for 20 months since her diagnosis, is still in remission. This case supports the utility of nivolumab in pediatric MPM.

A machine-learning-based prognostic strategy is developed in this paper for predicting the remaining useful life (RUL) of high-pressure packing in plunger-type hyper compressors. The proposed strategy applies principal component analysis (PCA) to identify three most important sensors out of 33 that seem relevant to the high-pressure packing. Singular value decomposition (SVD) is then performed with respect to chronological Hankel matrices reconstructed from one of these three sensor data, leakage flow. Normalized correlation coefficient between SVD eigenvalue vectors of chronological data is defined to come up with a health state assessment measurement. In order to enhance the prediction accuracy of RUL of the high-pressure packing, a linear-regression and two-term power series regression algorithms are both integrated into the NN (Neural Network) model. The effectiveness of the method is examined using the averaged difference (over thirteen data set) between the predicting and real failure events. The results showed that a maximum prediction RUL error of the model is less than 15 days and an averaged prediction RUL error is 7.23 days for 13 run-to-failure events. Furthermore, a more recent test was performed using the on-line data to examine the health states of four identical packing.

A mathematical formulation of a Linear Complementarity Problem (LCP) is presented for the 3D mixed beam-solid contact problem with the Mohr-Coulomb friction. The contact problems arising from the pile base and shaft are of linear and nonlinear complementarity problems, respectively. First, the latter is transformed into two LCPs, and then, all the LCPs are recast into a system of Fischer-Burmeister functions. Therefore, the mixed beam-solid contact problem can be solved by Newton’s method. The proposed method is validated by the numerical examples of a pile under axial compressive and tensile loads, which clearly shows that the numerical results are in good agreement with the field test results.