Explore the vast range of titles available.

Birthing in a hospital with on-site surgical facilities (co-located care) is considered preferable for neonates with surgical conditions. However, it may not always be feasible. Whether transfer of surgical neonates from birth hospital to a surgical facility affects the outcomes of this cohort is unclear. We conducted a systematic review to investigate the association of birth location/transfer with all-cause mortality and disability among neonates with congenital/acquired surgical conditions. Data Sources from PubMed, Embase, CINAHL, and Web of Science were searched till December 2024. Studies from high-income countries (HICs) comparing infants transferred to a surgical center for surgery versus infants born and operated in a co-located care facility were included. Random effects model was used for meta-analysis. The quality of studies and certainty of evidence were assessed using Newcastle-Ottawa Scale and the GRADE framework respectively. The primary outcomes of interest were all-cause mortality and neurodevelopmental impairment at latest follow up. A total of 61 studies from 20 HICs were included. Compared to co-located care, transfer for surgery did not increase the odds of risk-adjusted and crude mortality in neonates with congenital diaphragmatic hernia [adjusted odds ratio (aOR):0.86 (0.49 to 1.49), 5 studies, 8366 infants; crude OR:0.68 (0.51 to 0.91, i.e., decreased mortality), 22 studies, 12970 infants], critical congenital heart disease [aOR:0.79 (0.42 to 1.48), 3 studies, 13485 infants; OR:1.04 (0.66 to 1.64), 10 studies, 14447 infants], surgical necrotizing enterocolitis [aOR:0.99 (0.61 to 1.61), 4 studies, 5891 infants; OR:1.03 (0.64 to 1.65), 5 studies, 5915 infants], gastroschisis [aOR:1.07 (0.68 to 1.68), 2 studies, 5294 infants; OR:0.80 (0.48 to 1.35), 11 studies, 8708 infants], tracheo-oesophageal fistula [aOR:0.97 (0.39 to 2.39), 1 study, 937 infants; OR:0.62 (0.37 to 1.04), 4 studies, 4050 infants], congenital or perinatal intestinal conditions [OR:2.69 (0.26 to 28.34), 4 studies, 1799 infants]. Neurodevelopmental outcomes between the groups were comparable in the three studies that reported this outcome. Whilst many included studies were of good quality, certainty of evidence was very low due to their observational design and heterogeneity. In conclusion, transfer of neonates from the birth hospital to another facility for surgical intervention was not associated with increased risk of mortality or disability. The evidence from this comprehensive meta-analysis would be useful for clinicians, parents and health policy makers. Systematic review registration: PROSPERO CRD 42024565651.

Tumor hypoxia induced alterations in the epigenetic landscape and alternative splicing influence cellular adaptations. PRMT5 is a type II protein arginine methyltransferase that regulates several tumorigenic events in many cancer types. However, the regulation of PRMT5 and its direct implication on aberrant alternative splicing under hypoxia remains unexplored. In this study, we observed hypoxia-induced upregulation of PRMT5 via the CTCF in human breast cancer cells. Further, PRMT5-mediated symmetric arginine dimethylation H4R3me2s and H3R8me2s directly regulated the alternative splicing of TCF3 . Under hypoxia, PRMT5-mediated histone dimethylation at the intronic conserved region (ICR) present between TCF3 exon 18a and exon 18b recruits DNMT3A, resulting in DNA methylation. DNA methylation at the TCF3 -ICR is recognized and bound by MeCP2 resulting in RNA-Pol II pausing, promoting the recruitment of the negative splicing factor PTBP1 to the splicing locus of TCF3 pre-mRNA. PTBP1 promotes the exclusion of exon 18a which results in the production of the pro-invasive TCF3-18B (E47) isoform which promotes EMT and invasion of breast cancer cells under hypoxia. Collectively, our results indicate PRMT5-mediated symmetric arginine dimethylation of histones regulates alternative splicing of TCF3 gene thereby enhancing EMT and invasion in breast cancer hypoxia.

ObjectiveTo evaluate the effect of minimising blood sampling losses on red blood cell (RBC) transfusion-related outcomes in preterm infants <37 weeks’ gestation.Study designWe searched PubMed, Embase, Web of Science and Google Scholar from inception to October 2024 for studies that evaluated sampling stewardship practices (SSP) in preterm infants during initial hospitalisation. Two authors independently screened articles that evaluated one or more sampling approaches to minimise blood loss or non-invasive methods to avoid sampling losses. Meta-analysis was conducted using a random effects model.ResultsEighteen studies (4 randomised controlled trials (RCTs) and 14 non-randomised studies) were included. Five studies used umbilical cord blood sampling, four used protocol-based sampling and two used retransfusion of sampled blood back to the infant as an SSP. Sampling care bundles were used in seven studies. Meta-analysis showed that SSP reduced early RBC transfusion rates (RCTs: Relative risk(RR) =0.50, 95% CI 0.36, 0.68; non-RCTs: RR=0.78, 95% CI 0.69, 0.90), the average number of transfusions per infant (RCTs: mean difference=−0.4 transfusions, 95% CI −0.68, –0.05; non-RCTs: standardised mean difference=−0.40, 95% CI −0.55, –0.25) and the rates of multiple transfusions (non-RCTs: RR=0.51, 95% CI 0.42, 0.62). There were no significant effects on mortality and other morbidities. Certainty of evidence was high for transfusion-related outcomes and moderate for other outcomes.ConclusionSSPs are associated with a significant reduction in RBC transfusion rates among very and extremely preterm infants. Large RCTs are required to assess the effects of SSP on other important outcomes.PROSPERO registration numberCRD42024539665.

BackgroundCerebral palsy is a common and a lifelong disabling neurodevelopmental disorder, we attempted to address the relative lack of evidence on the role of Trihexyphenidyl in the management of dystonia in children with cerebral palsyObjectivesTo study the short-term effect of trihexyphenidyl on dystonia and motor functions in children with newly diagnosed Cerebral Palsy.MethodsA randomized, double-blinded, placebo-controlled, parallel-group trial was conducted in consecutive children aged 6 months-5 years at a tertiary care hospital. Following baseline evaluation, the study participants were randomized into two groups and were started on medication. Assessments were performed at baseline, 3, 6, and 12weeks. A total of 50 children completed the study.ResultsAfter 12weeks of medication, statistically significant improvement in median scores of GDS was seen in 10 body regions in the intervention group as compared to only 4 body regions in the control group and significant improvement in GMFM 88 in both the groups. The motor status assessed using GMFCS showed that there was a reduction in GMFCS level in 4 children in the intervention group as compared to 1 child in the control group. DQ calculated using EDP-2 showed a significant change in the intervention group (p-value 0.026) at the end of 12 weeks but no change in the control group (p-value 0.218). However, no statistically significant difference was seen in the median change in outcome scores between the two groups.ConclusionsThis study could not document a statistically significant change between the two groups for the effect of trihexyphenidyl. A larger placebo-controlled trial, preferably multi-centric and with a longer follow-up period is needed to provide definitive results regarding the place of trihexyphenidyl in the management of dystonia in children with Cerebral Palsy.

The hypoxic milieu is a critical modulator of aerobic glycolysis, yet the regulatory mechanisms existing between the key glycolytic enzymes in hypoxic cancer cells are largely unexplored. In particular, M2 isoform of pyruvate kinase (PKM2) − the rate-limiting enzyme of glycolysis, is well-known to confer adaptive advantages under hypoxia. Herein, we report a non-canonical role of PKM2 in functioning as a co-activator of HIF-1α to govern the transcription of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). Nuclear PKM2 enhances HIF-1α and p300 occupancy at PFKFB3 hypoxia responsive elements (HREs) resulting in its upregulation. Consequently, absence of nuclear PKM2 fails to recruit HIF-1α which activates an opportunistic occupancy of HIF-2α at PFKFB3 HREs. Enhanced binding of HDAC3 also occurs in the absence of PKM2 which prevents HIF-2α from efficiently inducing PFKFB3 to hamper proliferation of hypoxic breast cancer cells. In addition, clinical relevance of the study has been investigated by demonstrating that Shikonin blocks nuclear translocation of PKM2 to suppress PFKFB3 expression. Furthermore, MCF7 cells-derived xenograft tumors in mice exhibited substantial tumor growth inhibition when treated with shikonin, highlighting the vitality of targeting PKM2. Taken in concert, this work provides novel insights into contributions of PKM2 in modulating hypoxic transcriptome and a previously unreported molecular axis exhibited by the hypoxic breast cancer cells for ensuring the maintenance of PFKFB3 expression essential for achieving high glycolytic flux.Competing Interest StatementThe authors have declared no competing interest.

AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that regulates energy homeostasis at cellular and organismal levels. It has been shown to affect several steps of breast cancer progression in a context-dependent manner. However, its role in normal mammary gland development and physiology remains ill-explored. Here, we show that AMPK expression and activity increased within murine mammary epithelia from puberty to pregnancy with highest levels during lactation, and then declined during involution. In ex vivo cultures of mammary epithelial cells (MECs) in organotypic scaffolds, treatment with lactogenic hormone prolactin (PRL) enhanced AMPK expression and activity. To understand the role of AMPK on mammary morphogenesis in vivo, we generated mice with conditional knockout of AMPKα isoforms α1 and α2 (AMPKα KO) in MECs. AMPKα KO mammary glands showed accelerated alveolar development with increased epithelial content of both luminal and myoepithelial lineages, suggestive of hyperproliferation. AMPKα KO mice also showed elevated beta-casein expression during pregnancy and lactation. These observations were phenocopied upon treatment of ex vivo cultivated wild-type MECs with a cognate AMPK inhibitor. AMPKα null MECs showed increased phosphorylated STAT5 which is known to drive alveologenesis downstream of prolactin signaling. Our study identifies a novel interplay between AMPK and PRL-STAT5 signaling that determines mammary alveologenesis and differentiation. Competing Interest Statement The authors have declared no competing interest.

Data cleaning is a process of detecting, correcting, or removing errors and inconsistencies from data in order to improve the quality of data. Data can be classified into two types, namely structured and unstructured. Standard techniques and tools are available to handle structured data. Most of the data generated in today's world is unstructured. A graph database stores data in the form of nodes and relationships between the nodes. Neo4j is a graph database tool which is accessed using the Cypher query language. We define and implement an extensive set of cleaning algorithms for removal of duplicate entries, errors and other inconsistencies in data in Neo4j. We conclude with the validation of these cleaning algorithms using data visualization techniques using excel graphs. The visualized results of the data before and after applying the cleaning algorithms proves the effectiveness of the proposed cleaning algorithms.

Tumor hypoxia induced alterations in the epigenetic landscape and alternative splicing influence cellular adaptations. PRMT5 is a type II protein arginine methyltransferase that regulates several tumorigenic events in many cancer types. However, the regulation of PRMT5 and its direct implication on aberrant alternative splicing under hypoxia remains unexplored. In this study, we observed hypoxia induced upregulation of PRMT5 via the CCCTC binding factor, CTCF. Further, PRMT5-mediated symmetric arginine dimethylation H4R3me2s and H3R8me2s directly regulated the alternative splicing of Transcription Factor 3 (TCF3). Under hypoxia, PRMT5-mediated histone dimethylation at the intronic conserved region (ICR) present between TCF3 exon 18a and exon 18b recruits DNA methyltransferase 3A (DNMT3A), resulting in DNA methylation. DNA methylation at the TCF3-ICR is recognized and bound by Methyl CpG binding protein (MECP2) resulting in RNA-Pol II pausing, promoting the recruitment of the negative splicing factor PTBP1 to the splicing locus of TCF3 mRNA. PTBP1 promotes the exclusion of exon 18a which results in the production of the pro-invasive TCF3-18B (E47) isoform which promotes EMT and invasion of breast cancer cells under hypoxia. Collectively, our results indicate PRMT5-mediated symmetric arginine dimethylation of histones regulates alternative splicing of TCF3 gene thereby enhancing EMT and invasion in breast cancer hypoxia.

Natural control of limb motion is continuous and progressively adaptive to individual intent. While intuitive interfaces have the potential to rely on the neuromuscular input by the user for continuous adaptation, continuous volitional control of assistive devices that can generalize across various tasks has not been addressed. In this study, we propose a method to use spatiotemporal ultrasound features of the rectus femoris and vastus intermedius muscles of able-bodied individuals for task-invariant learning of continuous knee kinematics during steady-state and transient ambulation. The task-invariant learning paradigm was statistically evaluated against a task-specific paradigm for the steady-state (1) level-walk, (2) incline, (3) decline, (4) stair ascent, and (5) stair descent ambulation tasks. The transitions between steady-state stair ambulation and level-ground walking were also investigated. It was observed that the continuous knee kinematics can be learned using a task-invariant learning paradigm with statistically comparable accuracy to a task-specific paradigm. Statistical analysis further revealed that incorporating the temporal ultrasound features significantly improves the accuracy of continuous estimations (p < 0.05). The average root mean square errors (RMSEs) of knee angle and angular velocity estimation were 7.06 and 53.1/sec, respectively, for the task-invariant learning compared to 6.00 and 51.8/sec for the task-specific models. High accuracy of continuous task-invariant paradigms overcome the barrier of task-specific control schemes and motivate the implementation of direct volitional control of lower-limb assistive devices using ultrasound sensing, which may eventually enhance the intuitiveness and functionality of these devices towards a \"free form\" control approach.