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The present study describes a 7-year-old male child who had attended the Pediatric Oncology Clinic of the Regional Cancer Centre, Thiruvananthapuram, Kerala, India, and was pathologically confirmed to have B-Acute Lymphoblastic Leukemia (B-ALL). Conventional cytogenetics analysis at diagnosis showed the presence of a double Philadelphia chromosome and the karyotype of the case was 47, XY, t(9;22)(q34;q11.2), + der(22)t(9;22). FISH, done as a molecular confirmation of the translocation, t(9;22)(q34;q11.2), and this case showed an additional fusion signal that confirms the presence of double Ph. As far as we are aware, this represents the initial and only occurrence of an abnormality report regarding the double Philadelphia chromosome in pediatric B-ALL within India. The double Philadelphia chromosome in B-ALL has a very poor prognosis despite aggressive treatment with chemotherapy. This study reveals the importance of conventional and molecular cytogenetic analysis in risk stratification and prognosis prediction of pediatric B-ALL. The risk stratification based on the conventional and molecular cytogenetic analysis may be taken into consideration for deciding the treatment strategy for each patient. [ABSTRACT FROM AUTHOR]

Anaplastic large-cell lymphoma (ALCL) constitutes 10–15% of non-Hodgkin lymphoma in children. With short-course chemotherapy, outcome has improved up-to 90% in developed-countries. There is limited-data on outcome of pediatric ALCL treated with ALCL99 protocol from low-middle income countries. Children ≤14 years, diagnosed with ALCL between 1st January 2007 and 31st December 2016 were analyzed. Details regarding clinical-presentation and treatment were recorded and outcome was analyzed. Fourteen-children were diagnosed. Median-age was 114 months (range 24 – 162 months). Male:female ratio was 3.6:1. Stage-I, II and III disease was seen in three (21.4%), three (21.4%), and eight (57.1%) children, respectively. Low, standard and high-risk disease was seen in two (14.2%), six (42.9%) and six (42.9%), respectively. All children were treated using ALCL99 protocol. Three (21.4%) children had disease-progression/relapse and five (35.7%) died (three from treatment-related mortality, and two from disease). At median follow-up of 54-months, four-year EFS and OS were 64.3% and 64.3%, respectively. Log-rank test demonstrated female gender (p = 0.005), stage-III disease (p < 0.001), visceral-organ involvement (p = 0.035), high-risk disease (p = 0.016) and, serum albumin ≤3.5 g/dL (p = 0.031) associated with significantly worse 4-year EFS. Cox-regression analysis demonstrated female gender associated with poor EFS (p = 0.02) and female gender and visceral-organ involvement associated with poor OS (p = 0.02, p = 0.011, respectively). Good survival could be achieved for children with ALCL using uniform treatment protocol in a resource-limited setting, especially among low and standard-risk children. Female-sex, high-risk disease, stage-III disease, visceral organ involvement and low albumin levels were associated with poor outcome, however these findings need to be corroborated in larger studies. [ABSTRACT FROM AUTHOR]

Membrane distillation has gained significant interest as a promising technology for treating high-salt wastewater. However, membranes with large and nonuniform pore structures are prone to wetting, which compromises their salt rejection efficiency. In this study, a highly uniform porous poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) membrane was designed and prepared through the mixed solvent phase separation (MSPS) method, which was utilized in direct contact membrane distillation to treat salt concentration solutions as high as 5.85 wt%. The results showed 13 % polymer concentration, 26 % octane concentration, and 90 s of cooling duration exhibited an optimal structure with an average pore size of 53 ± 3 nm, a surface porosity of 24.79 %, and a liquid entry pressure (LEP) value of 3.5 bar. The optimum MSPS PVDF-HFP membrane demonstrated a vapor flux of 27 kg m−2 h−1 and high salt rejection (more than 99.94 %), superior than that of the controlled NIPS membrane with nonuniform pore sizes and lower surface porosity. This desalination performance is comparable with the commercial PTFE membrane (99.68 %, 29 kg m−2 h−1) featuring an order of magnitude higher pore sizes and greater LEP. Importantly, the MSPS PVDF-HFP membrane maintained its high performance over the duration of a long-term experiment (>140 h). [Display omitted] • Uniformly porous PVDF-HFP membranes were prepared via the MSPS method. • An average pore size of 53 ± 3 nm and a surface porosity of 24.79 % were observed. • A vapor flux of 27 kg m2 h−1 with more than 99.94 % salt rejection was achieved. • The optimum membrane achieves comparable performance to the commercial membranes. [ABSTRACT FROM AUTHOR]

Robotic right live donor hepatectomy (r‐LDRH) has been reported with reduced morbidity compared to open donor right hepatectomy (o‐LDRH) in few recent series. Nevertheless, its routine use is debated. We present a large series comparing pure r‐LDRH with o‐LDRH. Consecutive r‐LDRH performed from June 2018 to June 2020 (n = 102) were compared with consecutive donors undergoing o‐LDRH (n = 152) from February 2016 to February 2018, a period when r‐LDRH was not available at this center. Propensity score matched (PSM) analysis of 89 case‐control pairs was additionally performed. Primary endpoints were length of high dependency unit (HDU) and hospital stay and Clavien‐Dindo graded complications among donors. Although r‐LDRH took longer to perform (540 vs. 462 min, P <.001), the postoperative peak transaminases levels (P <.001), the length of HDU (3 vs. 4 days, P <.001), and hospital stay (8 vs. 9 days, P <.001) were lower in in donors undergoing r‐LDRH. Clavien‐Dindo graded complications were similar (16.67% in r‐LDRH and 13.16% in o‐LDRH). The rates of early allograft dysfunction (1.6% vs. 3.3%), bile leak (14.7% vs. 10.7%), and 1‐year mortality (13.7% vs. 11.8%) were comparable between r‐LDRH and o‐LDRH recipients. PSM analysis yielded similar results between the groups. These data support the safety and feasibility of r‐LDRH in select donors. [ABSTRACT FROM AUTHOR]

Because of retina abnormalities of diabetic patients, the most common vision‐threatening disease is diabetic retinopathy (DR). The DR diagnosis and prevention are challenging tasks as they may lead to vision loss. According to the literature analysis, the shortcomings in existing studies, such as failed to reduce the feature dimension, higher execution time, and higher computational cost, unable to tune the hyper‐parameters, such as a number of hidden layers and learning rate, more computational complexities, higher cost, and so forth, during DR classification. To tackle these problems, we proposed a deep long‐ and short‐term memory (LSTM) in a neural network with Red Fox optimization (deep LSTM‐RFO) algorithm for DR classification. The four major components involved in the proposed methods are image preprocessing, segmentation, feature extraction, and classification. At first, an adaptive histogram equalization and histogram equalization model performs the fundus image preprocessing, thereby neglecting the noise and improving the contrast level of an image. Next, an adaptive watershed segmentation model effectively segments the lesion region based on the optic disc color and size of hemorrhages. At the third stage, we have extracted statistical, intensity, color, and shape features. Finally, the single normal class with three abnormal classes such as mild non‐proliferative diabetic retinopathy, moderate NPDR, and severe NPDR are accurately classified using the deep LSTM‐RFO algorithm. Experimentally, the MESSIDOR, STARE, and DRIVE datasets are used for both training and validation. MATLAB software performs the implementation process with respect to various evaluation criteria used. However, the proposed method accomplished superior performance, such as 98.45% specificity, 96.78% sensitivity, 97.92% precision, 96.89% recall, and 97.93% F‐score results in terms of DR classification than previous methods. [ABSTRACT FROM AUTHOR]

Background: Autism is more prevalent in males than in females. Hypotheses related to the extreme male brain theory of autism suggest that heightened androgen exposure during early development contributes to autistic traits. Whilst prior research focused mostly on the prenatal period, the current study tests the influences of androgen exposure during both the prenatal and the early postnatal periods on autistic traits during childhood. Methods: Anthropometric measures that are putative biomarkers of early androgen exposure were employed. Anogenital distance (AGD) was measured at birth and 3 months of age in boys and girls. Penile length at birth and 3 months of age was also measured in boys. When the children were 9–13 years old, a parent‐reported questionnaire (the 10‐item children's version of the Autism Spectrum Quotient; AQ‐10 Child) was used to assess autistic traits in 97 boys and 110 girls. Results: There were no significant associations between any of the AGD or penile length measures and scores on the AQ‐10 Child in boys, girls or the entire sample. Conclusions: The current study provides the first test of whether early measurements of AGD and/or penile length predict subsequent autistic traits. The current findings do not support a relationship between prenatal or early postnatal androgen exposure and autistic traits. The current study augments prior research showing no consistent relationship between early androgen exposure and autistic traits. [ABSTRACT FROM AUTHOR]

There is limited data regarding pediatric mixed phenotype acute leukemia (MPAL) and there is no global consensus on its management yet. In this retrospective study, we analyzed the outcomes of children diagnosed with MPAL at our institute. This study included children ≤ 14 years with MPAL who presented to a tertiary cancer center in India from January 1st 2009 to December 31st 2015. Over a seven-year period, 1390 patients with leukemia presented to our institute of which 22 patients (1.5%) had MPAL. Sixteen patients (72.7%) had B/myeloid leukemia, while 4 (18.1%) and 2 (9%) patients had T/myeloid and B/T leukemia respectively. Twenty-one patients were treated with a modified BFM ALL 95 protocol. 76.1% (n = 16) of patients had a good prednisolone response (GPR) on day 8 and end-of-induction (EOI) marrow was in remission in 90.5% (n = 19). A poor prednisolone response (PPR) on day 8 correlated with an inferior relapse-free survival (25% vs 79.5%, P=.025). The 4-year event-free survival (EFS) and overall survival (OS) for the entire group was 60.8% and 64.9% respectively while the EFS for patients who had a GPR and remission at the EOI (n = 15) was 80% as compared to 16.7% in patients with PPR or induction failure. Lymphoid directed chemotherapy is seen to have good survival outcomes in pediatric MPAL. However, a PPR on day 8 or a positive EOI marrow may be an indication for more aggressive treatment. [ABSTRACT FROM AUTHOR]

Study Question: Are maternal serum phthalate metabolite, phenol and paraben concentrations measured at 10-17 weeks of gestation associated with male infant genital developmental outcomes, specifically cryptorchidism, anogenital distance (AGD), penile length and testicular descent distance, at birth and postnatally?Summary Answer: Maternal serum bisphenol A (BPA) concentration at 10-17 weeks of gestation was positively associated with congenital or postnatally acquired cryptorchidism, and n-propyl paraben (n-PrP) concentration was associated with shorter AGD from birth to 24 months of age.What Is Known Already: Male reproductive disorders are increasing in prevalence, which may reflect environmental influences on foetal testicular development. Animal studies have implicated phthalates, BPA and parabens, to which humans are ubiquitously exposed. However, epidemiological studies have generated conflicting results and have often been limited by small sample size and/or measurement of chemical exposures outside the most relevant developmental window.Study Design, Size, Duration: Case-control study of cryptorchidism nested within a prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at 10-17 postmenstrual weeks of gestation from a single UK maternity unit between 2001 and 2009 and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 330 mothers of 334 male infants (30 with congenital cryptorchidism, 25 with postnatally acquired cryptorchidism and 279 unmatched controls) were included in the present analysis.Participants/materials, Setting, Methods: Maternal blood was collected at enrolment, and serum levels of 16 phthalate metabolites, 9 phenols (including BPA) and 6 parabens were measured using liquid chromatography/tandem mass spectrometry. Logistic regression was used to model the association of cryptorchidism with serum chemical concentrations, adjusting for putative confounders. Additionally, offspring AGD, penile length and testicular descent distance were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between serum chemical levels and these outcomes were tested using linear mixed models.Main Results and the Role Of Chance: Maternal serum BPA concentration was associated with offspring all-type cryptorchidism both when considered as a continuous exposure (adjusted odds ratio per log10 μg/l: 2.90, 95% CI 1.31-6.43, P =  0.009) and as quartiles (phet =  0.002). Detection of n-PrP in maternal serum was associated with shorter AGD (by 0.242 standard deviations, 95% CI 0.051-0.433, P =  0.01) from birth to 24 months of age; this reduction was independent of body size and other putative confounders. We did not find any consistent associations with offspring outcomes for the other phenols, parabens, and phthalate metabolites measured.Limitations, Reasons For Caution: We cannot discount confounding by other demographic factors or endocrine-disrupting chemicals. There may have been misclassification of chemical exposure due to use of single serum measurements. The cohort was not fully representative of pregnant women in the UK, particularly in terms of smoking prevalence and maternal ethnicity.Wider Implications Of the Findings: Our observational findings support experimental evidence that intrauterine exposure to BPA and n-PrP during early gestation may adversely affect male reproductive development. More evidence is required before specific public health recommendations can be made.Study Funding/competing Interest(s): This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), Newlife the Charity for Disabled Children, the Mothercare Group Foundation, Mead Johnson Nutrition and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. Visiting Fellowship (J.M.): Regional Programme 'Jiménez de la Espada' for Research Mobility, Cooperation and Internationalization, Seneca Foundation-Science and Technology Agency for the Region of Murcia (No. 20136/EE/17). K.O. is supported by the Medical Research Council (UK) (Unit Programme number: MC_UU_12015/2). The authors declare no conflict of interest. [ABSTRACT FROM AUTHOR]

Objective This article estimates the survival of children over 1 year of age diagnosed with metastatic neuroblastoma (NB) and treated in a nontransplant facility and determines the factors affecting survival. Materials and Method Case records of children aged 1 to 14 years treated for metastatic NB in our center from January 2008 to December 2017 were studied. Patients received conventional chemotherapy followed by surgery, radiotherapy, and metronomic maintenance chemotherapy. Results Eighty-nine patients with metastatic NB received treatment. Mean age was 3.5 years and male:female ratio was 1.1:1. The most common primary site was suprarenal (55%) and the most common site of metastasis was bone marrow (76%). Forty percent patients had multiple metastatic sites. Mean baseline lactate dehydrogenase (LDH) was 3724 U/L (range 303–16609 U/L) and 65% patients had LDH > 750 U/L. Fifty-three patients (59.6%) had good response to chemotherapy as evidenced by clearance of metastatic disease, but out of them, 43 patients (81%) progressed subsequently. Twenty-six patients underwent surgery and 12 patients received maintenance therapy. Seventy-four patients (86%) developed recurrence and all but one died. Median time to recurrence and death were 9 months (range 0–120 months) and 10 months (range 1–123 months), respectively. At a median follow-up of 72 months (range 15–135 months), 16 patients are alive, with 5-year disease-free survival and overall survival of 17.6 and 18.4%, respectively. Age, baseline LDH, chemotherapy regimen, and response to treatment significantly affected survival. Conclusion Younger age, lower baseline LDH, and good response to chemotherapy appear to confer survival advantage in pediatric metastatic NB, and may be used for optimization of treatment in the nontransplant setting in developing countries. [ABSTRACT FROM AUTHOR]

Background: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a well-known adverse effect of vincristine (VCR). Literature suggests that Asians are predisposed to develop SIADH following VCR administration. However, data regarding the occurrence of SIADH in children with malignancy are limited. This study aims to analyze the incidence, clinical picture, risk factors, management, and outcome of SIADH during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL).Materials and Methods: A prospective study was conducted among the 166 newly diagnosed pediatric ALL patients who were treated at a tertiary cancer center in India between January 2015 and December 2015. Patients who developed hyponatremia during induction chemotherapy were further investigated for SIADH.Results: The incidence of SIADH was 10.8% (n = 18) with a mean sodium level of 125 mEq/L (114-129 mEq/L). In the preceding 2 weeks, 72% of episodes were associated with the administration of two (n = 6) or three (n = 7) doses of VCR. One child presented with seizures. All the patients were managed with fluid restriction and only two patients required sodium correction with 3% saline. Girls older than 10 years of age showed a marginally significant correlation to develop SIADH (P-value = 0.059).Conclusion: We report a higher incidence of SIADH (10.8%) in Indian children, compared to that described in the literature, during induction chemotherapy for ALL. Regular monitoring of sodium levels during this period of chemotherapy is hence essential for the timely diagnosis and appropriate management of SIADH, which in turn will avert complications, including neurological symptoms secondary to SIADH. [ABSTRACT FROM AUTHOR]

Imatinib is a preferred drug for pediatric Chronic Myeloid Leukemia (CML). Long-term use has inhibitory effects on other tyrosine kinase pathways causing off-target complications such as growth impairment. Our aim was to evaluate impact of long-term use on longitudinal growth in children with CML in Kerala. We hypothesized that the impact would be lesser compared to Northern India as Kerala has the lowest rates of underweight and stunting, with a high literacy rate and per capita income. Children ≤14 years of age, diagnosed with CML and received imatinib for at least 1 year were included. Girls >9 years of age and boys >11 years were considered pubertal. Height Z scores were derived using WHO AnthroPlus. Paired t test compared difference of Z scores in prepubertal and postpubertal age groups. Height Z scores were compared with mid-parental height and sibling height Z scores. Thirty-six children were included (M = 21; F = 15). Median duration of imatinib exposure was 84 months. Decrease in longitudinal growth affected children in both prepubertal and postpubertal age groups. Decrease in height Z scores was more in prepubertal age group when imatinib therapy was initiated (p =.0018). Of 10 patients currently above 19 years (of whom 8 were in pubertal age and 2 in prepubertal age at start of imatinib) none are stunted. Patient's height Z scores was lesser compared to sibling height Z scores (p =.027). Children on continuous imatinib showed a significant stunting when treatment was initiated during prepubertal age. There is a catch-up of growth as the final height reached is within normal limits of WHO reference values. [ABSTRACT FROM AUTHOR]

Abstract We introduce a novel heteronuclear dipolar recoupling based on the R 2 1 − 1 symmetry, which uses the tanh/tan (tt) shaped pulse as a basic inversion element and is denoted R 2 1 − 1 (tt). Using first-order average Hamiltonian theory, we show that this sequence is non-γ-encoded and that it reintroduces the | m | = 1 spatial component of the Chemical Shift Anisotropy (CSA) of the irradiated isotope and its heteronuclear dipolar interactions. Using numerical simulations and one-dimensional (1D) 27Al-{31P} through-space D -HMQC (Dipolar Heteronuclear Multiple-Quantum Correlation) experiments on VPI-5, we compare the performances of this recoupling to those of other non-γ-encoded | m | = 1 heteronuclear recoupling schemes: REDOR (Rotational-Echo DOuble Resonance), SFAM (Simultaneous Frequency and Amplitude Modulation) and R 4 2 − 1 (tt). Such comparison indicates that the R 2 1 − 1 (tt) scheme is more robust to CSA, offset and radiofrequency field inhomogeneities than the other schemes. We take advantage of the high robustness of R 2 1 − 1 (tt) to CSA and offset to demonstrate the possibility to correlate the signals of 207Pb isotope with those of neighboring half-integer spin quadrupolar nuclei. Such approach is demonstrated experimentally by acquiring 11B-{207Pb} D -HMQC 2D spectra of Pb 4 O(BO 3) 2 crystalline powder. Graphical abstract (a) D-HMQC pulse sequence with Inverse-Recoupling performed with (b) REDORxy4, (c) SFAM, and (d) R21−1 (tt). Image 1 Highlights • Indirect recoupling decreases the t1-noise of D-HMQC. • SFAM recoupling is very efficient with D-HMQC if 1H is not detected. • R21−1 symmetry with tanh/tan shaped pulse as a basic inversion is more robust to large CSA in the indirect dimension. • 11B-{207 Pb} D-HMQC can be recorded with R21−1 (tanh/tan) recoupling. [ABSTRACT FROM AUTHOR]

Objective: IGF-I may be a marker of later metabolic and cardiovascular disease. The interactions between IGF-I and glucose metabolism are multifactorial, and there is potential confounding from several secondary effects. In this study, we examined the interaction between IGF-I and glucose metabolism in a large cohort of clinically well-characterized elderly twins. Design: A total of 303 twin pairs of the same gender (606 twins) were included in the study; 125 monozygotic and 178 dizygotic twin pairs. Methods: A clinical examination including a standard oral glucose tolerance test (OGTT) and anthropometric measurements was performed. Results: The heritability estimates were high for IGF-I and IGFBP-3 (h2: 0.65 (95% CI: 0.55-0.74) and 0.71 (0.48-0.94), respectively) and for insulin secretion (h2 = 0.56, P < 0.0001), whereas the heritability estimates for insulin sensitivity were low (h2 = 0.14, P = 0.11). In a multiple regression analysis (adjusting for age, gender and twin status), there was a negative association between IGF-I and insulin sensitivity (B: -0.13, SE 0.03, P < 0.0001) and IGF-I and disposition index (B: -0.05, SE 0.02, P < 0.001) in the entire cohort of 606 twins. The associations between IGF-I and both DI and HOMA-S did not differ between the DZ and MZ twins. Forty-five twin pairs were discordant for T2D, but the discordant twins had similar concentrations of IGF-I or IGFBP-3. Conclusions: There was a high heritability for IGF-I and IGFBP-3, but a low heritability for insulin secretion and insulin sensitivity in a group of elderly twins. In addition, we found a strong negative relationship between IGF-I and insulin sensitivity, which did not seem to be strongly genetically determined. [ABSTRACT FROM AUTHOR]

We introduce novel sequences using indirect detection to correlate quadrupolar nuclei and spin-1/2 isotopes, other than 1 H and 19 F. These sequences use γ-encoded symmetry-based R N n ν schemes that reintroduce the space component | m | = 1 of the heteronuclear dipolar coupling. These schemes can be applied to the indirectly detected spin in Dipolar-mediated Heteronuclear Multiple-Quantum Correlation ( D -HMQC) sequence or to the detected isotope in a novel sequence, named Dipolar-mediated Heteronuclear Universal-Quantum Correlation ( D -HUQC). We show that the signal of these sequences using γ-encoded recoupling does not depend on the γ Euler angle relating the inter-nuclear vector between the coupled spins to the MAS rotor-fixed frame. Therefore, the transfer efficiency of these sequences is in principle higher than that of D -HMQC methods using non-γ-encoded recoupling. Furthermore, numerical simulations show that the heteronuclear correlation experiments employing γ-encoded recoupling are more robust to Chemical Shift Anisotropy (CSA) of the irradiated spin and MAS frequency fluctuations. These results are confirmed by 13 C-{ 15 N} heteronuclear correlation on glycine and 31 P- 27 Al ones on VPI-5 and Na 7 (AlP 2 O 7 ) 4 PO 4 . These experiments indicate that R 16 3 5 recoupling produces the highest signal-to-noise ratio in heteronuclear correlation 2D experiments when the detected spin-1/2 nuclei are subject to large CSA. [ABSTRACT FROM AUTHOR]

Rasburicase is a novel drug used during the management of tumor lysis syndrome. In countries with limited resources, it is frequently given at a lower dose and only for the treatment of established tumor lysis syndrome and not as prophylaxis. A retrospective study was conducted in the department of pediatric oncology at a tertiary referral oncology center in south India to analyze the use of rasburicase over the past 3 years. Data of all the 18 children (< 14 years of age) who were given rasburicase for the management of hyperuricemia were collected and analyzed. With a mean rasburicase dose of 0.085 mg/kg, hyperuricemia was managed efficiently without the need for a hemodialysis in 16 children (88.8 %). The fall in mean serum uric acid levels after the administration of a single dose of rasburicase at 4, 24, and 48 hours was 31.18 %, 64.8 %, and 74.5 %, respectively. Rasburicase efficiently decreases the uric acid levels to a normal level within a short period. In resource-limited settings, rasburicase at a lower dose is a promising option for managing hyperuricemia in the event of a tumor lysis syndrome. [ABSTRACT FROM AUTHOR]

Study Question: What is the relationship between maternal paracetamol intake during the masculinisation programming window (MPW, 8-14 weeks of gestation) and male infant anogenital distance (AGD), a biomarker for androgen action during the MPW?Summary Answer: Intrauterine paracetamol exposure during 8-14 weeks of gestation is associated with shorter AGD from birth to 24 months of age.What Is Already Known: The increasing prevalence of male reproductive disorders may reflect environmental influences on foetal testicular development during the MPW. Animal and human xenograft studies have demonstrated that paracetamol reduces foetal testicular testosterone production, consistent with reported epidemiological associations between prenatal paracetamol exposure and cryptorchidism.Study Design, Size, Duration: Prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at ~12 post-menstrual weeks of gestation from a single UK maternity unit between 2001 and 2009, and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 676 delivered male infants and completed a medicine consumption questionnaire.Participants/materials, Setting, Method: Mothers self-reported medicine consumption during pregnancy by a questionnaire administered during the perinatal period. Infant AGD (measured from 2006 onwards), penile length and testicular descent were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between paracetamol intake during three gestational periods (<8 weeks, 8-14 weeks and >14 weeks) and these outcomes were tested by linear mixed models. Two hundred and twenty-five (33%) of six hundred and eighty-one male infants were exposed to paracetamol during pregnancy, of whom sixty-eight were reported to be exposed during 8-14 weeks. AGD measurements were available for 434 male infants.Main Results and the Role Of Chance: Paracetamol exposure during 8-14 weeks of gestation, but not any other period, was associated with shorter AGD (by 0.27 SD, 95% CI 0.06-0.48, P = 0.014) from birth to 24 months of age. This reduction was independent of body size. Paracetamol exposure was not related to penile length or testicular descent.Limitations, Reasons For Caution: Confounding by other drugs or endocrine-disrupting chemicals cannot be discounted. The cohort was not fully representative of pregnant women in the UK, particularly in terms of maternal ethnicity and smoking prevalence. There is likely to have been misclassification of paracetamol exposure due to recall error.Wider Implications Of the Findings: Our observational findings support experimental evidence that intrauterine paracetamol exposure during the MPW may adversely affect male reproductive development.Study Funding/competing Interests: This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), the Newlife Foundation for Disabled Children, the Evelyn Trust, the Mothercare Group Foundation, Mead Johnson Nutrition, and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. The authors declare no conflict of interest. [ABSTRACT FROM AUTHOR]

Abnormal foetal testis development has been proposed to underlie common disorders of the male reproductive system such as cryptorchidism, hypospadias, reduced semen quality and testicular germ cell tumour, which are regarded as components of a 'testicular dysgenesis syndrome'. The increasing trends and geographical variation in their incidence have been suggested to result from in utero exposure to environmental chemicals acting as endocrine disruptors. In rodents, the anogenital distance ( AGD), measured from the anus to the base of genital tubercle, is a sensitive biomarker of androgen exposure during a critical embryonic window of testis development. In humans, several epidemiological studies have shown alterations in AGD associated with prenatal exposure to several chemicals with potential endocrine disrupting activity. However, the link between AGD and androgen exposure in humans is not well-defined. This review focuses on the current evidence for such a relationship. As in rodents, a clear gender difference is detected during foetal development of the AGD in humans which is maintained thereafter. Reduced AGD in association with clinically relevant outcomes of potential environmental exposures, such as cryptorchidism or hypospadias, is in keeping with AGD as a marker of foetal testicular function. Furthermore, AGD may reflect variations in prenatal androgen exposure in healthy children as shorter AGD at birth is associated with reduced masculine play behaviour in preschool boys. Several studies provide evidence linking shorter AGD with lower fertility, semen quality and testosterone levels in selected groups of adults attending andrology clinics. Overall, the observational data in humans are consistent with experimental studies in animals and support the use of AGD as a biomarker of foetal androgen exposure. Future studies evaluating AGD in relation to reproductive hormones in both infants and adults, and to gene polymorphisms, will help to further delineate the effect of prenatal and postnatal androgen exposures on AGD. [ABSTRACT FROM AUTHOR]

Background/Aims: Physiological growth hormone (GH) secretion and insulin-like growth factor-I (IGF-I) levels are greater in young compared to older adults. We evaluated IGF-I levels and predictors of IGF-I responses in young adults on GH replacement. Design: From the KIMS database, 310 young adults (age 15-26 years) with severe GH deficiency related to childhood-onset disease and commenced on 'adult GH replacement' were identified. 'IGF-I responses' were estimated from first-year increments in IGF-I standard deviation scores (SDS) and adjusted for GH dose. Body composition was assessed by bioimpedance in 143 patients. Results: IGF-I levels increased markedly from baseline to 1 year of replacement (-3.75 ± 1.94 vs. -1.36 ± 1.86 SDS, p < 0.0001), but remained low compared to normative data despite dose titration. In multivariate models, IGF-I responses were positively associated with age [B (SE) SDS/(mg/m²); 0.52 (0.15), p = 0.0007] and BMI SDS [1.06 (0.25), p < 0.0001] and inverse-ly associated with female gender [-4.45 (0.79), p < 0.0001] and baseline IGF-I SDS [-1.44 (0.20), p < 0.0001]. IGF-I responses were positively associated with first-year increases in lean body mass (r = 0.19, p = 0.003) and haemoglobin A1c (r = 0.15, p = 0.031). Conclusions: Low IGF-I levels in young adults on treatment may reflect suboptimal GH replacement. Identification of predictors for IGF-I responses could lead to a more appropriate replacement strategy. Association between IGF-I responses and lean body mass suggests that maintaining age-appropriate IGF-I levels is important during therapy. [ABSTRACT FROM AUTHOR]

To compare the safety and efficacy of once-daily tacrolimus (ODT) versus twice-daily tacrolimus (BDT) in adult live donor liver transplantation (LDLT). In this open-labelled randomized trial, 174 adult patients undergoing LDLT were randomized into ODT or BDT, combined with basiliximab induction and mycophenolate mofetil (steroid-free regimen). Tacrolimus was started at a total dose of 1 mg and the trough level was aimed at 3–7 ng/ml. The primary endpoint was eGFR at 1,3- and 6 months post-transplant, using CKD- EPI equation. Secondary endpoints included biopsy-proven acute rejection (BPAR), metabolic complications, post-operative bilio-vascular complications and patient survival. There was no statistically significant difference in eGFR between the two groups at 6 months (ODT –96 ± 19, BDT –91 ± 21, p value-0.164). BPAR was comparable (18/84 in ODT, 19/88 in BDT, p value-0.981). For a similar dosage of tacrolimus, the median trough tacrolimus levels attained were significantly lower for ODT than BDT during the first-month post-transplant (p value-0.001). Metabolic complications due to immunosuppression, post-operative bilio-vascular complications and patient survival was similar between the two groups at 6 months. Once-daily tacrolimus has similar renal safety and efficacy as twice-daily tacrolimus when used in combination with basiliximab induction and mycophenolate in adult LDLT. [ABSTRACT FROM AUTHOR]

Abstract Background Angiosarcoma is an uncommon high-grade sarcoma in children. Visceral angiosarcoma involving the ovary is extremely rare. Because of the lack of recurrent cytogenetic alterations, histopathological identification of this uncommon tumor in unusual sites like the ovary demands pathologic expertise. Complete surgical resection and radiotherapy are the chief treatment modalities determining survival, with chemotherapy contributing a minor role. Case We discuss a 11-year-old prepubertal girl who presented with primary angiosarcoma of the ovary. Summary and Conclusion Early realization of such exceptional presentations of these tumors is needed to achieve the best treatment outcome. [ABSTRACT FROM AUTHOR]

Precursor B-cell lymphoblastic lymphoma (LBL) occurring as a primary bone tumor is a rare clinical presentation in children, and data regarding this condition are limited to small case series or a few individual case reports. We report two pediatric cases of precursor B-cell LBL of the bone. The tumor cells from bone biopsies of both patients were seen to be positive for leukocyte common antigen (LCA), terminal deoxynucleotidyl transferase, CD10, CD20 and weakly positive for CD99. Bone marrow studies were normal. They were treated according to the modified Berlin-Frankfurt-Münster acute lymphoblastic leukemia high-risk protocol. The first patient has completed treatment including local radiotherapy and has been disease free for the past 10 years. The second patient has recently completed treatment and shows good response. [ABSTRACT FROM AUTHOR]

Ultrafiltration (UF) is a promising membrane process to remove surfactant-stabilized oil emulsions from produced water (PW). However, UF membranes prepared by conventional methods have suffered from low permeate flux and are susceptible to fouling due to the sparsity of pores on the surface. In this study, we used our recently developed mixed solvent phase separation (MSPS) method to fabricate a highly porous poly (vinylidene fluoride) (PVDF) ultrafiltration membrane for the treatment of produced water. The prepared MSPS PVDF membrane showed an asymmetric high-porous structure with a surface porosity of 23.66% and a narrow pore size distribution of 40 ± 19 nm. The MSPS PVDF membrane showed almost complete oil removal and high oily water permeance above 300 L m−2 h−1·bar−1 even after 72 h of continuous testing, which is an order of magnitude higher than the commercial PVDF membranes. In addition, the MSPS PVDF membrane showed excellent regeneration and recovery capabilities with a flux recovery ratio of 97% without any chemical cleaning, making the process economically and environmentally more viable. Moreover, we achieved optimal membrane performance without any further surface modification processes. [Display omitted] • High-porous PVDF membranes with 23.7% surface porosity was prepared by MSPS method. • Ultrafiltration of produced water showed flux >300 LMH/Bar even after 75 h. • Excellent antifouling properties with >97% flux recovery and 99.99% TOC removal. • Easy flux recovery by a low-pressure DI water backwash without chemical additives. [ABSTRACT FROM AUTHOR]

Fibrous nanosilica (KCC-1) oxynitrides are promising solid-base catalysts. Paradoxically, when their nitrogen content increases, their catalytic activity decreases. This counterintuitive observation is explained here for the first time using 15N-solid-state NMR spectroscopy enhanced by dynamic nuclear polarization. [ABSTRACT FROM AUTHOR]

Fibrous nanosilica (KCC-1) oxynitrides are promising solid-base catalysts. Paradoxically, when their nitrogen content increases, their catalytic activity decreases. This counterintuitive observation is explained here for the first time using 15N-solid-state NMR spectroscopy enhanced by dynamic nuclear polarization. [ABSTRACT FROM AUTHOR]

Background: Short children born small for gestational age (SGA) are treated with a GH dose based on body size, but treatment may lead to high levels of IGF1. The objective was to evaluate IGF1 titration of GH dose in contrast to current rc dosing strategies. Methods: In the North European Small-for-Gestational-Age Study (NESGAS), 92 short pre-pubertal children born SGA were w randomised after 1 year of high-dose GH treatment (67 μg/kg per day) to three different regimens: high dose (67 μg/kg per day), low dose (35 μg/kg per day) or IGF1 titration. Results: The average dose during the second year of the randomised trial did not differ between the IGF1 titration group (38 μg/kg per day, S.D. 0.019) and the low-dose group (35 mg/kg per day, S.D. 0.002; P=0.46), but there was a wide variation in the IGF1 titration group (range 10-80 mg/kg per day). The IGF1 titration group had significantly lower height gain (0.17 SDS, S.D. 0.18) during the second year of the randomised trial compared with the high-dose group (0.46 SDS, S.D. 0.25), but not significantly lower than the low-dose group (0.23 SDS, S.D. 0.15; P=0.17). The IGF1 titration group had lower IGF1 levels after 2 years of the trial (mean 1.16, S.D. 1.24) compared with both the low-dose (mean 1.76, S.D. 1.48) and the high-dose (mean 2.97, S.D. 1.63) groups. Conclusion: IGF1 titration of GH dose in SGA children proved less effective than current dosing strategies. IGF1 titration resulted in physiological IGF1 levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF1 resistance and highlights the heterogeneity of short SGA children. [ABSTRACT FROM AUTHOR]

Background: Anogenital distance (AGD) in animals is a sensitive biomarker of fetal endocrine disruption and the associated testicular dysgenesis syndrome (TDS). However, AGD in human infants with cryptorchidism and hypospadias, which are potential manifestations of TDS during childhood, is not clearly described. Objective: Our aim was to compare AGD in boys with cryptorchidism or hypospadias against normative data. Methods: Boys with isolated cryptorchidism (n = 71, age 13.4 ± 5.8 months) or hypospadias (n = 81, age 11.4 ± 6.2 months) were recruited from a tertiary center for measurement of AGD and penile length; they were compared with 487 healthy full-term boys from a birth cohort by deriving age-specific standard deviation scores (SDS). Results: Boys with cryptorchidism were older (p = 0.048) compared with boys with hypospadias. Boys with hypospadias had shorter mean AGD and penile length SDS than healthy boys (both p < 0.0001). Mean AGD and penile length SDS values in boys with cryptorchidism were longer than mean values in boys with hypospadias (both p < 0.01) and shorter than mean values in healthy boys (both p < 0.0001). Mean penile length SDS decreased as the severity of hypospadias increased (ptrend = 0.078). Conclusions: In the study population, AGD and penile length were reduced in boys with hypospadias or cryptorchidism relative to normative data derived from a longitudinal birth cohort. The findings support the use of AGD as a quantitative biomarker to examine the prenatal effects of exposure to endocrine disruptors on the development of the male reproductive tract. [ABSTRACT FROM AUTHOR]

Objective: Developmental programming alters growth and metabolic outcome in children born small for gestational age (SGA). We explored insulin and glucose metabolism in SGA children treated with a fixed GH dose over 1 year. Methods: In the North European Small for Gestational Age Study (NESGAS), 110 short SGA children received GH at 67 µg/kg/day for 1 year. Insulin secretion was assessed by acute insulin response (AIR), insulin sensitivity (IS) by HOMA and disposition index (DI) by insulin secretion adjusted for IS. Results: First-year GH therapy led to increases in height and IGF-I standard deviation score (SDS), and reductions in IS (p < 0.0001). Compensatory increases in AIR (p < 0.0001) were insufficient and resulted in reduced DI (p = 0.032). Children in the highest IGF-I SDS tertile at baseline were the least insulin sensitive at baseline (p = 0.024) and 1 year (p = 0.006). IGF-I responses after 1 year were positively related to AIR (r = 0.30, p = 0.007) and DI (r = 0.29, p = 0.005). Conclusion: In SGA children treated with a high GH dose for 1 year, baseline IGF-I levels were related to IS whilst gains in height and IGF-I responses were associated with insulin secretion. Defining heterogeneity in IGF-I in SGA children may be useful in predicting growth and metabolic response. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: The terminally-crosslinked sulfonated poly(ether sulfone) block copolymer (SPES-b) was developed for use as a proton exchange membrane in DMFC applications. The properties of the membrane prepared from SPES-b were compared with those of its non-crosslinked counterpart (SPES-bn) and Nafion®-117. The membrane displayed a well-defined morphology due to phase separation between the hydrophobic and hydrophilic ionic units in the SPES-b block copolymer. The terminally-crosslinked SPES-b membrane yielded a high proton conductivity of 0.09 S/cm and a low methanol permeability of 5.3 × 10−8 cm2/s at 20 °C, and the membrane displayed excellent dimensional, mechanical, hydrolytic, and oxidative stabilities. [Copyright &y& Elsevier]

Abstract: An ethyl imidazolium-functionalized poly(arylene ether sulfone) (EI-PES) block copolymer was prepared as a novel anion exchange membrane. The EI-PES polymer was synthesized by polycondensation between the F- and OH-terminated oligomers, followed by benzylic bromination and imidazolium functionalization (homogeneous functionalization). The quaternary ammonium-functionalized PES (QA-PES) was also prepared by heterogeneous functionalization, and the properties were compared with EI-PES. The membrane obtained from EI-PES showed a well-defined phase separated morphology between hydrophobic and hydrophilic ionic units of the block copolymer. An IEC of 1.45 meq/g with hydroxide conductivity of 0.03 S/cm at r.t. was observed for EI-PES. The EI-PES membrane also displayed excellent dimensional, thermal, mechanical and chemical stabilities. [Copyright &y& Elsevier]

Abstract: A novel terminally crosslinked block SPES-b membrane was prepared using an azide-assisted thermal curing of sulfonated multiblock poly(arylene ether sulfone). The membrane morphologies and conductivities were investigated as a function of temperature. The crosslinked block SPES-b membrane showed higher proton conductivities than Nafion® both at 20°C (0.09S/cm) and 100°C (0.77S/cm). High temperatures induced significant conduction enhancements and morphological changes for SPES-b. [Copyright &y& Elsevier]

According to the multistep model of cell migration, chemokine receptor engagement (step 2) triggers conversion of rolling interactions (step 1) into firm adhesion (step 3), yielding transendothelial migration. We recently reported that glycosyltransferase-programmed stereosubstitution (GPS) of CD44 on human mesenchymal stem cells (hMSCs) creates the E-selectin ligand HCELL (hematopoietic cell E-selectin/L-selectin ligand) and, despite absence of CXCR4, systemically administered HCELL+hMSCs display robust osteotropism visualized by intravital microscopy. Here we performed studies to define the molecular effectors of this process. We observed that engagement of hMSC HCELL with E-selectin triggers VLA-4 adhesiveness, resulting in shear-resistant adhesion to ligand VCAM-1. This VLA-4 activation is mediated via a Rac1/Rap1 GTPase signaling pathway, resulting in transendothelial migration on stimulated human umbilical vein endothelial cells without chemokine input. These findings indicate that hMSCs coordinately integrate CD44 ligation and integrin activation, circumventing chemokine-mediated signaling, yielding a step 2-bypass pathway of the canonical multistep paradigm of cell migration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Anogenital distance (AGD) is sexually dimorphic in rodents and humans, being 2- to 2.5-fold greater in males. It is a reliable marker of androgen and antiandrogen effects in rodent reproductive toxicologic studies. Data on AGD in humans are sparse, with no longitudinal data collected during infancy. OBJECTIVE: This study was designed to determine AGD from birth to 2 years in males and females and relate this to other anthropometric measures. MATERIALS AND METHODS: Infants were recruited from the Cambridge Baby Growth Study. AGD was measured from the center of the anus to the base of the scrotum in males and to the posterior fourchette in females. Measurements were performed at birth and at 3, 12, 18, and 24 months of age. RESULTS: Data included 2,168 longitudinal AGD measurements from 463 male and 426 female fullterm infants (median = 2 measurements per infant). Mean AGD (± SD) at birth was 19.8 ± 6.1 mm in males and 9.1 ± 2.8 mm in females (p < 0.0001). AGD increased up to 12 months in both sexes and in a sex-dimorphic pattern. AGD was positively correlated with penile length at birth (r = 0.18, p = 0.003) and the increase in AGD from birth to 3 months was correlated with penile growth (r = 0.20, p = 0.001). CONCLUSION: We report novel, longitudinal data for AGD during infancy in a large U.K. birth cohort. AGD was sex dimorphic at all ages studied. The availability of normative data provides a means of utilizing this biological marker of androgen action in population studies of the effects of environmental chemicals on genital development. [ABSTRACT FROM AUTHOR]

Condensation of 2-amino-3-carboxyethyl-4,5,6,7-tetrahydrobenzo[b]thiophene with carbonyl compounds such as isatin, o-hydroxyacetophenone or benzoin in 1:1 ratio in ethanol medium yielded three distinctly different heterocyclic Schiff bases viz. 2-(N-indole-2-one)amino-3-carboxyethyl-4,5,6,7-tetrahydrobenzo[b]thiophene (ISAT), 2-(N- o-hydroxyacetophenone)amino- 3-carboxyethyl-4,5,6,7-tetrahydro-benzo[b]thiophene (HAAT) or 2-(N-benzoin)amino-3-carboxyethyl-4,5,6,7-tetrahydrobenzo[b]thiophene (HBAT) respectively. These ligands formed well defined complexes with lanthanum(III) chloride under suitable conditions. The ligands and the complexes have been characterized on the basis of elemental analyses, molar conductance measurements, UV-visible, IR and proton NMR spectral studies. Kinetics and mechanism of the thermal decomposition of the ligands and the metal complexes have been studied using non-isothermal thermogravimetry. Kinetic parameters were calculated for each step of the decomposition reactions using Coats-Redfern equation. The rate controlling process for all the ligands and complexes is random nucleation with the formation of one nucleus on each particle (Mampel equation). Relative thermal stabilities of the ligands and the metal complexes have been compared. [ABSTRACT FROM AUTHOR]

The article presents a case of a 36-year-old woman with gestational diabetes who was in her second pregnancy. Congenital brain tumor should be considered in the differential diagnosis of intracranial hemorrhage especially in the absence of other predisposing factors. Computed tomography scanning is useful in further evaluation of such cases and should enable the precise diagnosis to be made.

CD44 is a cell surface receptor for the extracellular matrix macromolecule hyaluronan. In addition, CD44 mediates the endocytosis of hyaluronan leading to its subsequent degradation within lysosomes. Using model systems of COS-7 and Flp-293 cells, we demonstrate that the association of CD44 with lipid rafts is essential for the endocytosis of hyaluronan but not the extracellular binding. Further, we demonstrate that palmitoylation of CD44 on two highly conserved cysteine residues is essential for the association with lipid rafts as determined by density gradient ultracentrifugation. Mutations of either cysteine residues or pretreatment of cells with the palmitic acid analog 2-bromopalmitate, reduced the [³H]palmitic acid incorporation into CD44 and prevented CD44-lipid rafts association. Preventing CD44 palmitoylation had no effect on the binding of hyaluronan but inhibited hyaluronan internalization. The turnover of the CD44 receptor itself was also affected by blocking its association with lipid rafts. Using cycloheximide to prevent de novo protein synthesis, palmitoylation-deficient cysteine mutants underwent slower turnover from cell surface compared with the palmitoylation-intact wild type, as determined by immunofluorescence and Western blotting. These results indicate that palmitoylation of CD44 is a critical driving determinant to CD44 association with lipid rafts and, concomitantly, the rates of hyaluronan endocytosis and CD44 turnover from cell surface. [ABSTRACT FROM AUTHOR]

Congenital Adrenal Hyperplasia (CAH) is a group of genetic disorders that affect the adrenal glands. CAH manifests in abnormal levels of cortisol and androgens and is accompanied by white matter alterations. However, no CAH study has specifically targeted the corpus callosum, the brain's largest white matter fiber tract. To bridge that gap in the literature, we investigated callosal morphology in 53 individuals with CAH and 53 matched controls (66 women, 40 men). In addition to calculating areas for seven callosal subsections, we estimated the callosal thickness at 100 equidistant points. All statistical analyses were conducted while co-varying for age and total brain volume and applying corrections for multiple comparisons. There were no significant effects of biological sex and no significant group-by-sex interactions. However, there was a significant effect of group, both for area measures and thickness estimates, indicating smaller dimensions within the callosal splenium and isthmus in people with CAH. Our findings corroborate previous studies highlighting white matter alterations in CAH and may suggest that callosal integrity is compromised due to potentially adverse effects of glucocorticoids, a standard treatment for both men and women with CAH. [ABSTRACT FROM AUTHOR]

Nanoporous polyethersulfone (PES) membranes with high surface porosity and uniform pore size distribution were prepared by combining the phase separation in NMP/nonane mixed solvent system with the traditional nonsolvent induced phase inversion process. The effects of PES concentration, nonane concentration, evaporation time, casting solution temperature, and varied mixed solvent systems on the porous PES membrane surface morphology were thoroughly investigated and optimized. The optimized nanoporous PES membrane showed a high surface porosity with a uniform pore size of 20 nm, rendering an exceptional molecular weight cut-off of as low as 100 k Dalton. In addition, the membrane exhibited a significant molecular size exclusion with water permeance of 121 LMH bar−1, bovine serum albumin (BSA) protein rejection of 60.1%, and γ-globulin protein rejection of 99.5% at 0.5 bar, respectively, demonstrating the potential of the as-prepared nanoporous PES membrane for application in protein separation. [Display omitted] • PES membranes with high surface porosity were prepared by the MSPS method. • NMP/nonane system demonstrated a UCST phase behavior. • Asymmetric membrane structure was created by combining MSPS with NIPS. • Promising protein separation was demonstrated on PES membranes. [ABSTRACT FROM AUTHOR]

Simple Summary: Lineage plasticity is the ability of cells to transform from one cell type to another and is an important part for tissue repair and for maintenance of homeostasis. Unfortunately, the very same processes can be corrupted in cancer when the molecular checkpoints controlling the process are compromised; as a result of which treatment resistance and disease recurrence can emerge. It can be triggered by treatment received and has been seen across solid and liquid tumors. This review discusses the factors that control different manifestations of lineage plasticity in various cancer types and more importantly, discusses ideas to potentially revert this phenomenon. Lineage plasticity, the switching of cells from one lineage to another, has been recognized as a cardinal property essential for embryonic development, tissue repair and homeostasis. However, such a highly regulated process goes awry when cancer cells exploit this inherent ability to their advantage, resulting in tumorigenesis, relapse, metastasis and therapy resistance. In this review, we summarize our current understanding on the role of lineage plasticity in tumor progression and therapeutic resistance in multiple cancers. Lineage plasticity can be triggered by treatment itself and is reported across various solid as well as liquid tumors. Here, we focus on the importance of lineage switching in tumor progression and therapeutic resistance of solid tumors such as the prostate, lung, hepatocellular and colorectal carcinoma and the myeloid and lymphoid lineage switch observed in leukemias. Besides this, we also discuss the role of epithelial-mesenchymal transition (EMT) in facilitating the lineage switch in biphasic cancers such as aggressive carcinosarcomas. We also discuss the mechanisms involved, current therapeutic approaches and challenges that lie ahead in taming the scourge of lineage plasticity in cancer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of CamAPS FX hybrid closed-loop (HCL) automated insulin delivery in very young children with type 1 diabetes (T1D) on caregivers' well-being, fear of hypoglycemia, and sleepiness.Research Design and Methods: We conducted a multinational, open-label, randomized crossover study. Children (age 1-7 years) with T1D received treatment for two 4-month periods in random order, comparing HCL with sensor augmented pump (control). At baseline and after each treatment period, caregivers were invited to complete World Health Organization-Five Well-Being Index, Hypoglycemia Fear Survey, and Epworth Sleepiness Scale questionnaires.Results: Caregivers of 74 children (mean ± SD age 5 ± 2 years and baseline HbA1c 7.3 ± 0.7%; 42% female) participated. Results revealed significantly lower scores for hypoglycemia fear (P < 0.001) and higher scores for well-being (P < 0.001) after HCL treatment. A trend toward a reduction in sleepiness score was observed (P = 0.09).Conclusions: Our results suggest better well-being and less hypoglycemia fear in caregivers of very young children with T1D on CamAPS FX HCL. [ABSTRACT FROM AUTHOR]

We show how 27Al–13C proximities in the microporous metal–organic framework MIL-100(Al) can be probed using advanced 27Al–13C NMR methods boosted by Dynamic Nuclear Polarization. [ABSTRACT FROM AUTHOR]

We show how the 29Si NMR signals of dispersed inorganic nanoparticles of laponite® can be enhanced by Dynamic Nuclear Polarization (DNP). The direct DNP enhances the signals of 29Si nuclei near unpaired electrons, whereas the indirect DNP via1H enhances the signals of more remote sites. [ABSTRACT FROM AUTHOR]

The basic helix-loop-helix (bHLH) transcription factors inhibitor of differentiation 1 (Id1) and inhibitor of differentiation 3 (Id3) (referred to as Id) have an important role in maintaining the cancer stem cell (CSC) phenotype in the triple-negative breast cancer (TNBC) subtype. In this study, we aimed to understand the molecular mechanism underlying Id control of CSC phenotype and exploit it for therapeutic purposes. We used two different TNBC tumor models marked by either Id depletion or Id1 expression in order to identify Id targets using a combinatorial analysis of RNA sequencing and microarray data. Phenotypically, Id protein depletion leads to cell cycle arrest in the G0/G1 phase, which we demonstrate is reversible. In order to understand the molecular underpinning of Id proteins on the cell cycle phenotype, we carried out a large-scale small interfering RNA (siRNA) screen of 61 putative targets identified by using genomic analysis of two Id TNBC tumor models. Kinesin Family Member 11 (Kif11) and Aurora Kinase A (Aurka), which are critical cell cycle regulators, were further validated as Id targets. Interestingly, unlike in Id depletion conditions, Kif11 and Aurka knockdown leads to a G2/M arrest, suggesting a novel Id cell cycle mechanism, which we will explore in further studies. Therapeutic targeting of Kif11 to block the Id1–Kif11 axis was carried out using small molecular inhibitor ispinesib. We finally leveraged our findings to target the Id/Kif11 pathway using the small molecule inhibitor ispinesib in the Id+ CSC results combined with chemotherapy for better response in TNBC subtypes. This work opens up exciting new possibilities of targeting Id targets such as Kif11 in the TNBC subtype, which is currently refractory to chemotherapy. Targeting the Id1–Kif11 molecular pathway in the Id1+ CSCs in combination with chemotherapy and small molecular inhibitor results in more effective debulking of TNBC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We aimed to evaluate the longer-term safety and efficacy of hybrid closed-loop (CL) therapy in very young children with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Following a 16-week multinational, randomized crossover trial comparing hybrid CL with sensor-augmented pump (SAP) therapy in 74 very young children aged 1–7 years with T1D, participants were invited to an extension phase using CL for a further 18 months. Outcomes were compared with the primary-phase SAP period and primary-phase CL period. RESULTS: After the primary study phase, 60 participants were eligible to enroll in the extension. Of these, 49 consented (mean ± SD age 6.6 ± 1.5 years) to continue use of CL for 18 months. Percentage time in range (TIR) 3.9–10.0 mmol/L was 8.4 percentage points (95% CI 6.7–10.1; P < 0.001) higher, while HbA1c was 0.4% ([5.0 mmol/mol], 95% CI 0.3–0.6 [3.7–6.2]; P < 0.001) lower during the CL extension phase compared with primary-phase SAP period. At 18 months, mean HbA1c was 6.7 ± 0.5% and TIR was 70 ± 7%, compared with 6.7 ± 0.5% and 71 ± 6% in the primary-phase CL period. Time in hypoglycemia (<3.9 mmol/L) was similar between CL extension phase and both primary-phase SAP (P = 0.31) and CL periods (P = 0.70). There were two severe hypoglycemia events and one other serious adverse event during the extension phase. One unexpected serious adverse device effect occurred. CONCLUSIONS: Use of the Cambridge hybrid CL system led to sustained improvements in glycemic control lasting more than 18 months in very young children with T1D. [ABSTRACT FROM AUTHOR]

Mixed Matrix Membranes (MMMs) made from a porous covalent triazine piperazine polymer (CTPP) as filler embedded in poly ether-block-amide (PEBAX® 1657) were studied for the separation of CO 2 /N 2 and CO 2 /CH 4 gas systems. At a loading rate of 0.025 wt%, significant improvement was achieved for both CO 2 permeability (from 53 to 73 barrer) and selectivity (from 51 to 79 for CO 2 /N 2 and from 17 to 25 for CO 2 /CH 4) that were measured at 293 K and 3 bars. Results of FTIR, DSC, WAXS, and SEM revealed a strong interaction between CTPP and PEBAX due to the high density of hydrogen bonding in CTPP, which led to chain rigidification of PEBAX at very low loading rate compared to other literature reported systems. On the other hand, CTPP contains rich nitrogen in the framework, which favourites the adsorption of CO 2 more than N 2 and CH 4. Hence, although the chain rigidification decreased the CO 2 adsorption sites in PEBAX matrix, the intrinsic porosity and high surface area of CTPP compensated the diffusivity and solubility which in turn improved the overall permeability and selectivity at a very low loading rate. CTPP is highly stable in acid, base, and high temperature up to 400 °C. Hence, this novel type material is a very promising filler for preparation of mixed matrix membranes for the separation of CO 2 /N 2 and CO 2 /CH 4 systems. Image 1 • MMMs prepared from a covalent porous polymer filler CTPP in polymer PEBAX. • Strong interactions between CTPP and PEBAX were discovered. • Multiple effects in CTPP/PEBAX MMMs were discovered. • Enhancement in both permeability and selectivity was achieved at very low loading. [ABSTRACT FROM AUTHOR]

Summary: Modern portable communication devices require a compact antenna with superior performance and lower weight and size. The design and development of such a compact size antenna are a significant challenge for researchers. This proposed work compact slot‐based triangular patch antenna to work at the multiple resonance frequencies from 5 to 10 GHz using FR4 substrate is presented. The proposed antenna is simulated using High‐Frequency Structural Simulator (HFSS 2020R1). Simulated and fabricated antenna test results show that the proposed antenna can be suitably employed for the portable wireless transceivers in C and X bands. It has been inferred from the fabricated and measured results that the proposed slot‐based triangular patch antenna achieves the peak gain of 8 dBi and has excellent impedance matching properties such that return loss S11 is less than −10 dB and VSWR value is significantly closer to 1 at all the resonance frequencies. [ABSTRACT FROM AUTHOR]