Loss of the adhesion molecule CEACAM1 is associated with early biochemical recurrence in TMPRSS2:ERG fusion-positive prostate cancers.

Altered expression of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been linked to adverse tumor features in various cancer types. To better understand the role of CEACAM1 in prostate cancer, we analyzed a tissue microarray containing tumor spots from 17,747 prostate cancer patients by means of immunohistochemistry. Normal prostate glands showed intense membranous CEACAM1 positivity.

Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion.

Background: TFAP2D is a transcription factor important for modulating gene expression in embryogenesis. Its expression and prognostic role in prostate cancer has not been evaluated.

Methods: Therefore, a tissue microarray containing 17,747 prostate cancer specimens with associated pathological, clinical, and molecular data was analyzed by immunohistochemistry to assess the role of TFAP2D.

Manipulation of a spider peptide toxin alters its affinity for lipid bilayers and potency and selectivity for voltage-gated sodium channel subtype 1.7.

Huwentoxin-IV (HwTx-IV) is a gating modifier peptide toxin from spiders that has weak affinity for the lipid bilayer. As some gating modifier toxins have affinity for model lipid bilayers, a tripartite relationship among gating modifier toxins, voltage-gated ion channels, and the lipid membrane surrounding the channels has been proposed. We previously designed an HwTx-IV analogue (gHwTx-IV) with reduced negative charge and increased hydrophobic surface profile, which displays increased lipid bilayer affinity and activity at the voltage-gated sodium channel subtype 1.

Mechanical ventilation as a surrogate for diagnosing the onset of abdominal compartment syndrome (ACS) in severely burned patients (TIRIFIC-study Part II).

Intra-abdominal compartment syndrome (ACS) is a devastating complication in burn patients with a high mortality. Apart from high-volume resuscitation as known risk factor, also mechanical ventilation seems to influence the development of ACS. The TIRIFIC trial is a retrospective, matched-pair analysis.

MDM2, MDM4 and EGFR Amplifications and Hyperprogression in Metastatic Acral and Mucosal Melanoma.

Background: Mucosal and acral melanoma respond worse to immune checkpoint inhibitors (ICI) than cutaneous melanoma. as well as amplifications are supposed to be associated with hyperprogression on ICI in diverse cancers. We therefore investigated the response of metastatic acral and mucosal melanoma to ICI in regard to or amplifications and melanoma type.

Charge Transport in Sequence-Defined Conjugated Oligomers.

A major challenge in synthetic polymers lies in understanding how primary monomer sequence affects materials properties. In this work, we show that charge transport in single molecule junctions of conjugated oligomers critically depends on the primary sequence of monomers. A series of sequence-defined oligomers ranging from two to seven units was synthesized by an iterative approach based on the van Leusen reaction, providing conjugated oligomers with backbones consisting of para-linked phenylenes connected to oxazole, imidazole, or nitro-substituted pyrrole.

Noninvasive vagus nerve stimulation and the trigeminal autonomic reflex: An fMRI study.

Objective: The trigeminal autonomic reflex is a physiologic reflex that plays a crucial role in primary headache and particularly in trigeminal autonomic cephalalgias, such as cluster headache. Previous studies have shown that this reflex can be modulated by the vagus nerve, leading to an inhibition of the parasympathetic output of the reflex in healthy participants. The aim of the present study was to characterize neural correlates of the modulatory effect of noninvasive vagus nerve stimulation (nVNS) on the trigeminal autonomic reflex.

Quantification of Optic Nerve and Sheath Diameter by Transorbital Sonography: A Systematic Review and Metanalysis.

Background And Purpose: To date, normal values for optic nerve diameter (OND) and optic nerve sheath diameter (ONSD) for transorbital sonography (TOS) have only been reported by individual small-scale studies, exposing a great variability in the measurement of the OND and ONSD.

Methods: We performed a systematic review and metanalysis of available to date studies on TOS evaluation of adults without elevated intracranial pressure to provide an overview of the published literature, measuring methods and further specify normal values for OND and ONSD.

Results: In total, we included 39 studies with 2,927 healthy volunteers (mean age 36.

Laser and electron deflection from transverse asymmetries in laser-plasma accelerators.

We report on the deflection of laser pulses and accelerated electrons in a laser-plasma accelerator (LPA) by the effects of laser pulse front tilt and transverse density gradients. Asymmetry in the plasma index of refraction leads to laser steering, which can be due to a density gradient or spatiotemporal coupling of the laser pulse. The transverse forces from the skewed plasma wave can also lead to electron deflection relative to the laser.

The Thalamocortical Circuit of Auditory Mismatch Negativity.

Background: Mismatch negativity (MMN) is an extensively validated biomarker of cognitive function across both normative and clinical populations and has previously been localized to supratemporal auditory cortex. MMN is thought to represent a comparison of the features of the present stimulus versus a mnemonic template formed by the prior stimuli.

Methods: We used concurrent thalamic and primary auditory cortical (A1) laminar recordings in 7 macaques to evaluate the relative contributions of core (lemniscal) and matrix (nonlemniscal) thalamic afferents to MMN generation.

Single Molecule Molecular Inversion Probes for High Throughput Germline Screenings in Dystonia.

This study's aim was to investigate a large cohort of dystonia patients for pathogenic and rare variants in the gene, making use of a new, cost-efficient enrichment technology for NGS-based screening. Single molecule Molecular Inversion Probes (smMIPs) were used for targeted enrichment and sequencing of all protein coding exons and exon-intron boundaries of the gene in 373 dystonia patients and six positive controls with known variants. Additionally, a rare-variant association study was performed.

Nuclear up regulation of the BRCA1-associated ubiquitinase BAP1 is associated with tumor aggressiveness in prostate cancers lacking the TMPRSS2:ERG fusion.

Loss of the putative tumor suppressor BAP1 is a candidate biomarker for adverse prognosis in many cancer types, but conversely for improved survival in others. Studies on the expression and prognostic role of BAP1 in prostate cancer are currently lacking. We used a tissue microarray of 17,747 individual prostate cancer samples linked with comprehensive pathological, clinical and molecular data and studied the immunohistochemical expression of BAP1.

Weaponisation 'on the fly': Convergent recruitment of knottin and defensin peptide scaffolds into the venom of predatory assassin flies.

Many arthropod venom peptides have potential as bioinsecticides, drug leads, and pharmacological tools due to their specific neuromodulatory functions. Assassin flies (Asilidae) are a family of predaceous dipterans that produce a unique and complex peptide-rich venom for killing insect prey and deterring predators. However, very little is known about the structure and function of their venom peptides.

Divalent cations promote TALE DNA-binding specificity.

Recent advances in gene editing have been enabled by programmable nucleases such as transcription activator-like effector nucleases (TALENs) and CRISPR-Cas9. However, several open questions remain regarding the molecular machinery in these systems, including fundamental search and binding behavior as well as role of off-target binding and specificity. In order to achieve efficient and specific cleavage at target sites, a high degree of target site discrimination must be demonstrated for gene editing applications.

Lentiform Nucleus Hyperechogenicity in Parkinsonian Syndromes: A Systematic Review and Meta-Analysis with Consideration of Molecular Pathology.

The hyperechogenicity of the substania nigra (SN) has been established as a valid finding in patients with Parkinson´s disease (PD), probably caused by an increased tissue iron concentration in the SN. The application of transcranial sonography (TCS) has been investigated for further echogenic basal ganglia alterations in patients with extrapyramidal movement disorders. Compared to PD, a hyperechogenic nucleus lentiformis (LN) has been reported to appear more frequently in atypical parkinsonian syndromes (aPS) such as the parkinsonian phenotype of multiple system atrophy (MSA-P) or the progressive supranuclear palsy (PSP).

Optimization of risk stratification for anticoagulation-associated intracerebral hemorrhage: net risk estimation.

Background: Every anticoagulation decision has in inherent risk of hemorrhage; intracerebral hemorrhage (ICH) is the most devastating hemorrhagic complication. We examined whether combining ischemic and hemorrhagic stroke risk in individual patients might provide a meaningful paradigm for risk stratification.

Methods: We enrolled consecutive patients with anticoagulation-associated ICH in 15 tertiary centers in the USA, Europe and Asia between 2015 and 2017.

Atrophy of optic nerve detected by transorbital sonography in patients with demyelinating diseases of the central nervous system.

Background And Purpose: Transorbital sonography (TOS) has emerged as promising imaging method for the diagnosis and follow-up of acute optic neuritis (ON). Available studies report an increase in the optic nerve diameter (OND) and the optic nerve sheath diameter (ONSD) in the case of a first episode of ON in the affected eye compared to either the contralateral unaffected eye or controls. However, the utility of TOS in the case of recurrent episodes of ON has never been assessed.

A Non-interventional Clinical Trial Assessing Immune Responses After Radiofrequency Ablation of Liver Metastases From Colorectal Cancer.

Radiofrequency ablation (RFA) is an established treatment option for malignancies located in the liver. RFA-induced irreversible coagulation necrosis leads to the release of danger signals and cellular content. Hence, RFA may constitute an endogenous tumor vaccination, stimulating innate and adaptive immune responses, including tumor-antigen specific T cells.

[Influence of extreme weather conditions on the deployment volume of emergency medical services].

Background: Due to global warming a worldwide increase in the frequency and intensity of heat waves have been forecast. In the context of the overall increasing number of emergency service calls, weather-induced effects on the number of calls are highly relevant. We evaluated the influence of extreme temperatures on emergency medical services.

Conformational dynamics and phase behavior of lipid vesicles in a precisely controlled extensional flow.

Lipid vesicles play a key role in fundamental biological processes. Despite recent progress, we lack a complete understanding of the non-equilibrium dynamics of vesicles due to challenges associated with long-time observation of shape fluctuations in strong flows. In this work, we present a flow-phase diagram for vesicle shape and conformational transitions in planar extensional flow using a Stokes trap, which enables control over the center-of-mass position of single or multiple vesicles in precisely defined flows [A.

Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders.

Objective: To investigate if patients with neuromyelitis optica spectrum disorder (NMOSD) develop subclinical visual pathway impairment independent of acute attacks.

Methods: A total of 548 longitudinally assessed full-field visual evoked potentials (VEP) of 167 patients with NMOSD from 16 centers were retrospectively evaluated for changes of P100 latencies and P100-N140 amplitudes. Rates of change in latencies (RCL) and amplitudes (RCA) over time were analyzed for each individual eye using linear regression and compared using generalized estimating equation models.

Meiosis: How Gambling Chromosomes Beat the Rules.

Selfish centromeres exploit asymmetric female meiosis to drive non-Mendelian segregation in their favor. Using inherent differences in drive propensity between mouse chromosomes, a new study reveals how proteins that modify chromatin states and microtubule stability enable this selfish behavior.

Enzymatic Ligation of a Pore Blocker Toxin and a Gating Modifier Toxin: Creating Double-Knotted Peptides with Improved Sodium Channel Na1.7 Inhibition.

Disulfide-rich animal venom peptides targeting either the voltage-sensing domain or the pore domain of voltage-gated sodium channel 1.7 (Na1.7) have been widely studied as drug leads and pharmacological probes for the treatment of chronic pain.

Ultrasound-guided rectus sheath block: an anatomic study in dog cadavers.

Objectives: To describe the ultrasound-guided rectus sheath block technique and the anatomical spread of two volumes of methylene blue injection in dog cadavers.

Study Design: Blinded, prospective, experimental cadaveric study.

Animals: A total of eight dog cadavers weighing 8.

Children who engaged in interpersonal problematic sexual behaviors.

Background: Over one-third of inappropriate sexual contact experienced by children is initiated by other children. Many studies examined child initiators (CIs) of interpersonal problematic sexual behaviors (IPSBs). This study uniquely links CI information with types of sexual contact as described by children they engaged in IPSBs.