bluuebunny/crossref_metadata_2025_split huggingface dataset:
NAA10 polyadenylation signal variants cause syndromic microphthalmia
Authors: Johnston Jennifer J , Williamson Kathleen A , Chou Christopher M , Sapp Julie C , Ansari Morad , Chapman Heather M , Cooper David N , Dabir Tabib , Dudley Jeffrey N , Holt Richard J , Ragge Nicola K , Schäffer Alejandro A , Sen Shurjo K , Slavotinek Anne M , FitzPatrick David R , Glaser Thomas M , Stewart Fiona , Black Graeme CM , Biesecker Leslie G 
Published: March 2019

BackgroundA single variant in NAA10 (c.471+2T>A), the gene encoding N-acetyltransferase 10, has been associated with Lenz microphthalmia syndrome. In this study, we aimed to identify causative variants in families with syndromic X-linked microphthalmia.MethodsThree families, including 15 affected individuals with syndromic X-linked microphthalmia, underwent analyses including linkage analysis, exome sequencing and targeted gene sequencing. The consequences of two identified variants in NAA10 were evaluated using quantitative PCR and RNAseq.ResultsGenetic linkage analysis in family 1 supported a candidate region on Xq27-q28, which included NAA10. Exome sequencing identified a hemizygous NAA10 polyadenylation signal (PAS) variant, chrX:153,195,397T>C, c.*43A>G, which segregated with the disease. Targeted sequencing of affected males from families 2 and 3 identified distinct NAA10 PAS variants, chrX:g.153,195,401T>C, c.*39A>G and chrX:g.153,195,400T>C, c.*40A>G. All three variants were absent from gnomAD. Quantitative PCR and RNAseq showed reduced NAA10 mRNA levels and abnormal 3′ UTRs in affected individuals. Targeted sequencing of NAA10 in 376 additional affected individuals failed to identify variants in the PAS.ConclusionThese data show that PAS variants are the most common variant type in NAA10-associated syndromic microphthalmia, suggesting reduced RNA is the molecular mechanism by which these alterations cause microphthalmia/anophthalmia. We reviewed recognised variants in PAS associated with Mendelian disorders and identified only 23 others, indicating that NAA10 harbours more than 10% of all known PAS variants. We hypothesise that PAS in other genes harbour unrecognised pathogenic variants associated with Mendelian disorders. The systematic interrogation of PAS could improve genetic testing yields.
Endovascular thrombectomy in pediatric patients with large vessel occlusion
Authors: Shoirah Hazem , Shallwani Hussain , Siddiqui Adnan H , Levy Elad I , Kenmuir Cynthia L , Jovin Tudor G , Levitt Michael R , Kim Louis J , Griauzde Julius , Pandey Aditya S , Gemmete Joseph J , Abruzzo Todd , Arthur Adam S , Elijovich Lucas , Hoit Daniel , Cheema Ahmed , Aghaebrahim Amin , Sauvageau Eric , Hanel Ricardo , Ringer Andrew J , Nascimento Fábio A , Kan Peter , Mocco J 
Published: March 2019

BackgroundPediatric acute ischemic stroke with underlying large vessel occlusion is a rare disease with significant morbidity and mortality. There is a paucity of data about the safety and outcomes of endovascular thrombectomy in these cases, especially with modern devices.MethodsWe conducted a retrospective review of all pediatric stroke patients who underwent endovascular thrombectomy in nine US tertiary centers between 2008 and 2017.ResultsNineteen patients (63.2% male) with a mean (SD) age of 10.9(6) years and weight 44.6 (30.8) kg were included. Mean (SD) NIH Stroke Scale (NIHSS) score at presentation was 13.9 (5.7). CT-based assessment was obtained in 88.2% of the patients and 58.8% of the patients had perfusion-based assessment. All procedures were performed via the transfemoral approach. The first-pass device was stentriever in 52.6% of cases and aspiration in 36.8%. Successful revascularization was achieved in 89.5% of the patients after a mean (SD) of 2.2 (1.5) passes, with a mean (SD) groin puncture to recanalization time of 48.7 (37.3) min (median 41.5). The mean (SD) reduction in NIHSS from admission to discharge was 10.2 (6.2). A good neurological outcome was achieved in 89.5% of the patients. One patient had post-revascularization seizure, but no other procedural complications or mortality occurred.ConclusionsEndovascular thrombectomy is safe and feasible in selected pediatric patients. Technical and neurological outcomes were comparable to adult literature with no safety concerns with the use of standard adult devices in patients as young as 18 months. This large series adds to the growing literature but further studies are warranted.
Endovascular mechanical thrombectomy for acute stroke in young children
Authors: Sun Lisa R , Felling Ryan J , Pearl Monica Smith 
Published: March 2019

BackgroundMechanical thrombectomy has emerged as a standard of care for acute stroke from large vessel occlusion in adults but remains controversial in children. Cerebral vessels are nearly adult size by 5 years of age but the technical feasibility of achieving recanalization in younger and smaller children with current endovascular tools remains unclear.ObjectiveTo systematically review the literature on mechanical thrombectomy for stroke in children less than 5 years of age.ResultsMechanical thrombectomy for acute stroke has been reported in 11 children under the age of 5 years (range 9 months to 4 years). The mean time from symptom onset to groin puncture was 12 hours (range 4–50 hours). Complete recanalization was achieved in 7/12 (58%) vessels attempted, and partial recanalization in 4/12 (33%). Two procedure related complications were reported, with small vessel size felt to be contributory to basilar vasospasm in one case. Favorable neurological outcomes were reported in 7 cases (64%).ConclusionsOur review of the literature demonstrates that mechanical thrombectomy for acute ischemic stroke may be feasible in carefully selected infants and young children less than 5 years of age using currently available devices. Efficacy in promoting better neurologic outcomes remains unproven, and other questions persist, including whether complications such as vasospasm occur more frequently in young children compared with adults. Further study is needed to determine the safety and efficacy of pediatric mechanical thrombectomy. These data suggest that young children should not be excluded from future studies or clinical treatment on the basis of age alone.
Impact of procedural time on clinical and angiographic outcomes in patients with acute ischemic stroke receiving endovascular treatment
Authors: Hassan Ameer E , Shariff Umar , Saver Jeffrey L , Goyal Mayank , Liebeskind David , Jahan Reza , Qureshi Adnan I 
Published: March 2019

BackgroundProcedural time in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy may affect clinical outcomes. We performed a pooled analysis of the effect of procedural time on clinical outcomes using data from three prospective endovascular treatment trials.ObjectiveTo examine the relationship between endovascular procedural time and clinical outcomes of patients with AIS following endovascular treatment.MethodsWe analyzed data from SWIFT, STAR, and SWIFT PRIME studies, including baseline characteristics: National Institutes of Health Stroke Scale (NIHSS) score on admission, intracranial hemorrhage rates, and modified Rankin Scale score at 3 months. The Thrombolysis in Cerebral Infarction (TICI) scale was used to grade postprocedure recanalization. We recorded two procedural time intervals: (1) symptom onset to groin puncture and (2) groin puncture to angiographic recanalization. A multivariate analysis was performed using a logistic regression model to analyze predictors of unfavorable outcome.ResultsWe analyzed 301 patients who had undergone endovascular treatment and had near-complete or complete recanalization (TICI 2b or 3). At 3 months, 122 patients (40.5%) had unfavorable outcomes. The rate of favorable outcomes was significantly higher when the procedural time was <60 min compared with ≥60 min (62% vs 45%, p=0.020). Predictors of unfavorable outcome at 3 months were age (unit 10 years, OR=0.62, 95% CI 0.46 to 0.82, p<0.001), onset to groin puncture time (unit hour, OR=0.61, 95% CI 0.48 to 0.77, p<0.001), groin puncture to recanalization (unit 10 min, OR=0.89, 95% CI 0.80 to 0.99, p=0.032), baseline NIHSS score (20–28 vs 8–10, OR=0.17, 95% CI 0.05 to 0.62, p=0.018), and collaterals (OR=1.48, 95% CI 1.04 to 2.10, p=0.029).ConclusionProcedural time in patients with stroke undergoing mechanical thrombectomy may be an important determinant of favorable outcomes in those with recanalization.
Choose to test: self-selected testing for sexually transmitted infections within an online service
Authors: Syred Jonathan , Holdsworth Gillian , Howroyd Chris , Spelman Kez , Baraitser Paula 
Published: March 2019

ObjectiveTo describe the outcomes of user-led, choice of test within an online sexual health service.MethodsWe analysed routinely collected data from a free, online sexual health service in Essex, UK that enabled users to select their tests. The service website provided information on all sexually transmitted infections, recommended a testing package based on sexuality and ethnicity, and invited users to modify this if they chose. Data on orders were analysed for the 6 months before (May–October 2016) and after (October–April 2017) implementation.ResultsWe compared 7550 orders from 6253 users before and 9785 orders from 7772 users after implementation. There was no difference in the proportion of chlamydia (p=0.57) or gonorrhoea (p=0.79) tests that were positive between the two periods. HIV and syphilis positives were too few in our sample during both periods for analysis. During implementation, men who have sex with men (530 users) were offered genital, rectal and oral chlamydia and gonorrhoea testing plus HIV and syphilis testing. In 17.2% of orders, users removed tests. Black or ethnic minority users excluding those who reported as men who have sex with men (805 users) were offered chlamydia, gonorrhoea and HIV testing. In 77.9% of orders, users added a test. All other users were offered chlamydia and gonorrhoea tests only. In 65.2% of orders, users added tests. We observed a reduction in orders of 3083 blood tests (31%).ConclusionUsers engaged with the ‘choose to test’ intervention. Although a majority added tests, the intervention was cost saving by reducing the HIV and syphilis tests ordered.
No temporal contrast enhancement of simple decreases in noxious heat
Authors: Beck Brianna , Gnanasampanthan Sahana , Iannetti Gian Domenico , Haggard Patrick 
Published: March 2019

Offset analgesia (OA) studies have found that small decreases in the intensity of a tonic noxious heat stimulus yield a disproportionately large amount of pain relief. In the classic OA paradigm, the decrease in stimulus intensity is preceded by an increase of equal size from an initial noxious level. Although the majority of researchers believe this temporal sequence of two changes is important for eliciting OA, it has also been suggested that the temporal contrast mechanism underlying OA may enhance detection of simple, isolated decreases in noxious heat. To test whether decreases in noxious heat intensity, by themselves, are perceived better than increases of comparable sizes, we used an adaptive two-interval alternative forced choice task to find perceptual thresholds for increases and decreases in radiant and contact heat. Decreases in noxious heat were more difficult to perceive than increases of comparable sizes from the same initial temperature of 45°C. In contrast, decreases and increases were perceived equally well within a common range of noxious temperatures (i.e., when increases started from 45°C and decreases started from 47°C). In another task, participants rated the pain intensity of heat stimuli that randomly and unpredictably increased, decreased, or remained constant. Ratings of unpredictable stimulus decreases also showed no evidence of perceptual enhancement. Our results demonstrate that there is no temporal contrast enhancement of simple, isolated decreases in noxious heat intensity. Combined with previous OA findings, they suggest that long-lasting noxious stimuli that follow an increase-decrease pattern may be important for eliciting the OA effect. NEW & NOTEWORTHY Previous research suggested that a small decrease in noxious heat intensity feels surprisingly large because of sensory enhancement of noxious stimulus offsets (a simplified form of “offset analgesia”). Using a two-alternative forced choice task where participants detected simple increases or decreases in noxious heat, we showed that decreases in noxious heat, by themselves, are no better perceived than increases of comparable sizes. This suggests that a decrease alone is not sufficient to elicit offset analgesia.
High-density extracellular probes reveal dendritic backpropagation and facilitate neuron classification
Authors: Jia Xiaoxuan , Siegle Joshua H. , Bennett Corbett , Gale Samuel D. , Denman Daniel J. , Koch Christof , Olsen Shawn R. 
Published: March 2019

Different neuron types serve distinct roles in neural processing. Extracellular electrical recordings are extensively used to study brain function but are typically blind to cell identity. Morphoelectrical properties of neurons measured on spatially dense electrode arrays have the potential to distinguish neuron types. We used high-density silicon probes to record from cortical and subcortical regions of the mouse brain. Extracellular waveforms of each neuron were detected across many channels and showed distinct spatiotemporal profiles among brain regions. Classification of neurons by brain region was improved with multichannel compared with single-channel waveforms. In visual cortex, unsupervised clustering identified the canonical regular-spiking (RS) and fast-spiking (FS) classes but also indicated a subclass of RS units with unidirectional backpropagating action potentials (BAPs). Moreover, BAPs were observed in many hippocampal RS cells. Overall, waveform analysis of spikes from high-density probes aids neuron identification and can reveal dendritic backpropagation. NEW & NOTEWORTHY It is challenging to identify neuron types with extracellular electrophysiology in vivo. We show that spatiotemporal action potentials measured on high-density electrode arrays can capture cell type-specific morphoelectrical properties, allowing classification of neurons across brain structures and within the cortex. Moreover, backpropagating action potentials are reliably detected in vivo from subpopulations of cortical and hippocampal neurons. Together, these results enhance the utility of dense extracellular electrophysiology for cell-type interrogation of brain network function.
Central mesencephalic reticular formation control of the near response: lens accommodation circuits
Authors: May Paul J. , Billig Isabelle , Gamlin Paul D. , Quinet Julie 
Published: March 2019

To view a nearby target, the three components of the near response are brought into play: 1) the eyes are converged through contraction of the medial rectus muscles to direct both foveae at the target, 2) the ciliary muscle contracts to allow the lens to thicken, increasing its refractive power to focus the near target on the retina, and 3) the pupil constricts to increase depth of field. In this study, we utilized retrograde transsynaptic transport of the N2c strain of rabies virus injected into the ciliary body of one eye of macaque monkeys to identify premotor neurons that control lens accommodation. We previously used this approach to label a premotor population located in the supraoculomotor area. In the present report, we describe a set of neurons located bilaterally in the central mesencephalic reticular formation that are labeled in the same time frame as the supraoculomotor area population, indicating their premotor character. The labeled premotor neurons are mostly multipolar cells, with long, very sparsely branched dendrites. They form a band that stretches across the core of the midbrain reticular formation. This population appears to be continuous with the premotor near-response neurons located in the supraoculomotor area at the level of the caudal central subdivision of the oculomotor nucleus. The central mesencephalic reticular formation has previously been associated with horizontal saccadic eye movements, so these premotor cells might be involved in controlling lens accommodation during disjunctive saccades. Alternatively, they may represent a population that controls vergence velocity. NEW & NOTEWORTHY This report uses transsynaptic transport of rabies virus to provide new evidence that the central mesencephalic reticular formation (cMRF) contains premotor neurons controlling lens accommodation. When combined with other recent reports that the cMRF also contains premotor neurons supplying medial rectus motoneurons, these results indicate that this portion of the reticular formation plays an important role in directing the near response and disjunctive saccades when viewers look between targets located at different distances.
Epigallocatechin-3-Gallate Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis via Suppression of Oxidant Stress and Apoptosis by Targeting Hypoxia-Inducible Factor-1α/ Angiopoietin-Like 4 Pathway
Authors: Liu Guoyong , He Liyu 
Published: March 2019

<b><i>Background:</i></b> Focal and segmental glomerular sclerosis (FSGS) is a common cause of nephrotic syndrome and end-stage renal disease. It has been reported that overproduction of reactive oxygen species (ROS) and cell apoptosis are associated with the development of FSGS. Epigallocatechin-3-gallate (EGCG) is a bioactive constituent accounting for more than 50% of the total catechins in green tea, which have anti-oxidative and anti-apoptotic effects. Based on this, this study was designed to evaluate the renoprotective effect of EGCG treatment on Adriamycin-induced FSGS. ­<b><i>Methods:</i></b> In C57BL/6 mice, Adriamycin nephropathy (AN) was induced by Adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then the mice were given with EGCG (20 mg/kg body weight) or YC-1 (Lificiguat, a specific inhibitor of hypoxia-inducible factor-1α [HIF-1α], 50 mg/kg body weight) or both intraperitoneally. Both the EGCG and YC-1 were given on the day of Adriamycin injection and continued for 6 weeks. The animals were organized into the following 5 groups for the animal experiments: the control group, the AN group, the AN + EGCG group, the AN + YC-1 group and the AN + EGCG + YC-1 group. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis. The HIF-1α and the angiopoietin-like 4 (ANGPTL4) expression were detected by Western blot, real-time PCR, immunohistochemistry or immunofluorescence. Dihydroethidium staining and NADPH oxidase 1 (Nox1) measurement were used to detect ROS production. Terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) staining and caspase-3 measurement was used to detect cell apoptosis. <b><i>Results:</i></b> When the animals were treated with Adriamycin, both the ROS production and TUNEL positive cells increased. Besides, the expression of HIF-1α, ANGPTL4, and caspase-3 were also up-regulated, while EGCG treatment could attenuate these changes. Interestingly, compared with treatment with YC-1 or EGCG alone, more pronounced inhibition of ANGPTL4, caspase-3 and Nox1 were obtained when YC-1 and EGCG were administered simultaneously. <b><i>Conclusion:</i></b> EGCG attenuates FSGS through the suppression of Oxidant Stress and apoptosis by targeting the HIF-1α/ANGPTL4 pathway.
INFRASTRUCTURE, RESOURCES, SERVICES EVALUATION AND GAP ANALYSIS OF INTEGRATED MATERNAL AND CHILD DEVELOPMENT SERVICES IN INDIA
Authors: Kaur S. , Gupta R. , Khan I. D. , Jindal S. , Prajapati S. , Makkar A. , Rajmohan K. S. 
Published: March 2019

Background. Integrated Child Development Services (ICDS) is an Indian community-centric government program organized under Anganwadi centres catering to supplementary nutrition, health and preschool education, primary healthcare, growth monitoring and counselling the children under six years old along with their mothers. It is the world’s largest outreach program in a developing country covering a population of 1.35 billion; the variations in service delivery were analysed involving cross-sectional rural and urban Anganwadi centers in New Delhi.
Methods. Data were collected by assessment of children and mothers, interview of Anganwadi workers and observation of service delivery parameters and conduction of activities. Infrastructural, beneficiaries, services and content were evaluated by a suitable pre-tested questionnaire based on the National Institute of Public Cooperation and Child Development (NIPCCD) evaluation proforma. The data was analysed by a descriptive statistics.
Results. Gaps were found in respect of infrastructure, resources, health and nutrition facilities especially at rural Anganwadi centre which was inadequate in terms of implementation of nutrition and health program, supplementary nutrition, preschool education and nutrition rehabilitation centre for existing beneficiaries. Both Anganwadi centres were not catering for new WHO growth standards and adolescent health.
Conclusions. Gaps found in respect of infrastructure, resources, health and nutrition facilities can affect performance of ICDS program and the services delivered by Anganwadi centres, which need a boost. Both urban and rural centres have a direct opportunity towards delivering adolescent health program focusing on nutrition and education of girls prior to their pregnancy, and adoption of new WHO growth standards.
OBESITY: A CAUSATIVE RISK FACTOR OF BREAST CANCER
Authors: Roy A. S. , Basu S. , Bandyopadhyay A. 
Published: March 2019

Background. Obesity, a global health burden and one of the most deleterious diseases have substantially increased prevalence attributable to changing lifestyle of modern times. Persuasive evidence indicates obesity as an independent prognostic factor for developing malignancy in the form of breast cancer particularly in post-menopausal women.
Objective. This review aims to focus in comprehensive manner on the biochemical, hormonal and immunological pathways governing the obesity linked breast cancer so that potential treatments may be improvised consequently to provide a cure to this menace, threatening the lives of many.
Methods. Literature review of published materials that provide examination of recent or current literature on problem of obesity.
Results. Increased body fatness, mainly visceral adiposity may account for predisposing an obese individual to the risk of encountering cancer although the mechanisms for such cancers may vary depending upon the organ affected. Metabolic and biochemical alterations influencing obesity related carcinogenesis, consisting of heightened oxidative stress and bodily inflammation levels with the concomitant rise in pro-inflammatory cytokines are discussed. Pertinent references about elevated levels of serum insulin, insulin-like growth factor, sex steroids and the imbalance in adipokines (adiponectin and leptin) are included as well.
Conclusions. Persuasive evidence indicates obesity as an independent prognostic factor for developing malignancy in the form of breast cancer particularly in post-menopausal women. Generation of novel and effective therapeutic interventions for combating the ailment along with positive lifestyle modifications may be improvised consequently to provide a cure to this menace, threatening the lives of many.