On-line bibliographic databases: relevant information retrieval on demand

Relevant and selective information can de readily sought by the users if they have sccess to on-line bibliographic databases. The right information is retrieved 'instantly' out of the computer-held bibliographic records from an extensive and comprehensive range of indexes and databases spread all over the world this technique

Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS.

Reactive astrocytes influence post-injury recovery, repair, and pathogenesis of the mammalian CNS. Much of the regulation of astrocyte reactivity, however, remains to be understood. Using genetic loss and gain-of-function analyses in vivo, we show that the conserved MAP3K13 (also known as leucine zipper-bearing kinase [LZK]) promotes astrocyte reactivity and glial scar formation after CNS injury. Inducible LZK gene deletion in astrocytes of adult mice reduced astrogliosis and impaired glial scar formation, resulting in increased lesion size after spinal cord injury. Conversely, LZK overexpression in astrocytes enhanced astrogliosis and reduced lesion size. Remarkably, in the absence of injury, LZK overexpression alone induced widespread astrogliosis in the CNS and upregulated astrogliosis activators pSTAT3 and SOX9. The identification of LZK as a critical cell-intrinsic regulator of astrocyte reactivity expands our understanding of the multicellular response to CNS injury and disease, with broad translational implications for neural repair

Birth data accessibility via primary care health records to classify health status in a multi-ethnic population of children: an observational study

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Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy in Patients with Early Onset Pancreatic Cancer: Clinical Outcomes and Toxicity

Purpose/Objective(s): Little is known on optimal management of patients with early onset pancreatic cancer (EOPC), including the role of radiation therapy. As such, we report on a cohort of patients with EOPC (age \u3c55 years) who was treated with neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT). Materials/Methods: This was a single institution retrospective review of patients with EOPC who were treated with upfront chemotherapy followed by SBRT with or without surgical resection. Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and treatment-related toxicity. Next-generation sequencing (NGS) was performed on select patient tumor specimens. Results: From 2016-2021, 47 patients met the inclusion criteria. Median age was 50.4 years (range, 36.4 – 54.7 years). Median induction chemotherapy duration was 4 months (range, 2.5 – 9 months). The majority (46/47, 97.9%) of patients received 33 Gy in 5 fractions. Following SBRT, 43 patients (91%) underwent surgical exploration, with extent of vascular involvement on post-SBRT imaging precluding exploration in 4 patients (9%). Gross resection was achieved in 33 patients (70.2%), with intraoperative metastatic disease precluding resection in 8 patients (17%) and intraoperative extent of vascular involvement of the primary tumor precluding resection in 4 patients (9%). Median OS, LPFS, DMFS, and PFS were 14.2 months, 11.6 months, 8.9 months, and 8.1 months respectively. Six-month and 1-year LPFS were 88.3% and 45.4%, respectively. Chemotherapy duration (\u3e 4 months) was associated with improved median OS (16.5 vs 10.1 months, p=0.005), LPFS (10.1 vs 4.9 months, p=0.002), DMFS (9.7 vs 5.2 months, p=0.014), and PFS (9.7 vs 5.2 months, p=0.020). Normalization of CA 19-9 (\u3c 34 vs \u3e 34 U/ml) after chemotherapy was associated with improved median DMFS (not reached vs 5.6 months, p=0.003) and PFS (11.3 vs 5.6 months, p=0.022). Grade 3+ rates of chemotherapy and radiation-related toxicity were 14.9% and 2.1% respectively. Clavien-Dindo 3b toxicity rate was 3.0%. A total of 15 patients underwent NGS, with mutations being found in KRAS (10/15, 66.7%), TP53 (7/15, 46.7%), NOTCH 1/2 (3/15, 20%), CDK2NA (2/15, 13.3%), and SMAD4(1/15, 6.7%). Conclusion: Multi-modality therapy for EOPC was administered with low toxicity, but outcomes remain suboptimal. Induction chemotherapy duration \u3e 4 months and normalization of CA 19-9 after chemotherapy were associated with improved outcomes, suggesting a role for extended durations of systemic therapy titrated to CA 19-9 response before transitioning to local therapy. The high rate of local failure and the low rate of grade 3+ toxicity also suggest a role for intensifying local therapy in this population, such as radiation dose escalation, expansion of the radiation target volume, and more aggressive surgical techniques

Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour

The mechanism of eukaryotic chemotaxis remains unclear despite intensive study. The most frequently described mechanism acts through attractants causing actin polymerization, in turn leading to pseudopod formation and cell movement. We recently proposed an alternative mechanism, supported by several lines of data, in which pseudopods are made by a self-generated cycle. If chemoattractants are present, they modulate the cycle rather than directly causing actin polymerization. The aim of this work is to test the explanatory and predictive powers of such pseudopod-based models to predict the complex behaviour of cells in chemotaxis. We have now tested the effectiveness of this mechanism using a computational model of cell movement and chemotaxis based on pseudopod autocatalysis. The model reproduces a surprisingly wide range of existing data about cell movement and chemotaxis. It simulates cell polarization and persistence without stimuli and selection of accurate pseudopods when chemoattractant gradients are present. It predicts both bias of pseudopod position in low chemoattractant gradients and-unexpectedly-lateral pseudopod initiation in high gradients. To test the predictive ability of the model, we looked for untested and novel predictions. One prediction from the model is that the angle between successive pseudopods at the front of the cell will increase in proportion to the difference between the cell's direction and the direction of the gradient. We measured the angles between pseudopods in chemotaxing Dictyostelium cells under different conditions and found the results agreed with the model extremely well. Our model and data together suggest that in rapidly moving cells like Dictyostelium and neutrophils an intrinsic pseudopod cycle lies at the heart of cell motility. This implies that the mechanism behind chemotaxis relies on modification of intrinsic pseudopod behaviour, more than generation of new pseudopods or actin polymerization by chemoattractant

Semi-automatic delineation of the spino-laminar junction curve on lateral X-ray radiographs of the cervical spine

Assessment of the cervical spine using X-ray radiography is an important task when providing emergency room care to trauma patients suspected of a cervical spine injury. In routine clinical practice, a physician will inspect the alignment of the cervical spine vertebrae by mentally tracing three alignment curves along the anterior and posterior sides of the cervical vertebral bodies, as well as one along the spinolaminar junction. In this paper, we propose an algorithm to semi-automatically delineate the spinolaminar junction curve, given a single reference point and the corners of each vertebral body. From the reference point, our method extracts a region of interest, and performs template matching using normalized cross-correlation to find matching regions along the spinolaminar junction. Matching points are then fit to a third order spline, producing an interpolating curve. Experimental results demonstrate promising results, on average producing a modified Hausdorff distance of 1.8 mm, validated on a dataset consisting of 29 patients including those with degenerative change, retrolisthesis, and fracture

Genome-wide mapping of Myc binding and gene regulation in serum-stimulated fibroblasts

The transition from quiescence to proliferation is a key regulatory step that can be induced by serum stimulation in cultured fibroblasts. The transcription factor Myc is directly induced by serum mitogens and drives a secondary gene expression program that remains largely unknown. Using mRNA profiling, we identify close to 300 Myc-dependent serum response (MDSR) genes, which are induced by serum in a Myc-dependent manner in mouse fibroblasts. Mapping of genomic Myc-binding sites by ChIP-seq technology revealed that most MDSR genes were directly targeted by Myc, but represented a minor fraction (5.5%) of all Myc-bound promoters (which were 22.4% of all promoters). Other target loci were either induced by serum in a Myc-independent manner, were not significantly regulated or were negatively regulated. MDSR gene products were involved in a variety of processes, including nucleotide biosynthesis, ribosome biogenesis, DNA replication and RNA control. Of the 29 MDSR genes targeted by RNA interference, three showed a requirement for cell-cycle entry upon serum stimulation and 11 for long-term proliferation and/or survival. Hence, proper coordination of key regulatory and biosynthetic pathways following mitogenic stimulation relies upon the concerted regulation of multiple Myc-dependent genes

Axial Higgs Mode Detected by Quantum Pathway Interference in RTe3

The observation of the Higgs boson solidified the standard model of particle physics. However, explanations of anomalies (e.g. dark matter) rely on further symmetry breaking calling for an undiscovered axial Higgs mode. In condensed matter the Higgs was seen in magnetic, superconducting and charge density wave(CDW) systems. Uncovering a low energy mode's vector properties is challenging, requiring going beyond typical spectroscopic or scattering techniques. Here, we discover an axial Higgs mode in the CDW system RTe3 using the interference of quantum pathways. In RTe3 (R=La,Gd), the electronic ordering couples bands of equal or different angular momenta. As such, the Raman scattering tensor associated to the Higgs mode contains both symmetric and antisymmetric components, which can be excited via two distinct, but degenerate pathways. This leads to constructive or destructive interference of these pathways, depending on the choice of the incident and Raman scattered light polarization. The qualitative behavior of the Raman spectra is well-captured by an appropriate tight-binding model including an axial Higgs mode. The elucidation of the antisymmetric component provides direct evidence that the Higgs mode contains an axial vector representation (i.e. a pseudo-angular momentum) and hints the CDW in RTe3 is unconventional. Thus we provide a means for measuring collective modes quantum properties without resorting to extreme experimental conditions

RNA-Containing Cytoplasmic Inclusion Bodies in Ciliated Bronchial Epithelium Months to Years after Acute Kawasaki Disease

Kawasaki Disease (KD) is the most common cause of acquired heart disease in children in developed nations. The KD etiologic agent is unknown but likely to be a ubiquitous microbe that usually causes asymptomatic childhood infection, resulting in KD only in genetically susceptible individuals. KD synthetic antibodies made from prevalent IgA gene sequences in KD arterial tissue detect intracytoplasmic inclusion bodies (ICI) resembling viral ICI in acute KD but not control infant ciliated bronchial epithelium. The prevalence of ICI in late-stage KD fatalities and in older individuals with non-KD illness should be low, unless persistent infection is common.Lung tissue from late-stage KD fatalities and non-infant controls was examined by light microscopy for the presence of ICI. Nucleic acid stains and transmission electron microscopy (TEM) were performed on tissues that were strongly positive for ICI. ICI were present in ciliated bronchial epithelium in 6/7 (86%) late-stage KD fatalities and 7/27 (26%) controls ages 9-84 years (p = 0.01). Nucleic acid stains revealed RNA but not DNA within the ICI. ICI were also identified in lung macrophages in some KD cases. TEM of bronchial epithelium and macrophages from KD cases revealed finely granular homogeneous ICI.These findings are consistent with a previously unidentified, ubiquitous RNA virus that forms ICI and can result in persistent infection in bronchial epithelium and macrophages as the etiologic agent of KD