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Electronic Decoupling and Hole-Doping of Graphene Nanoribbons on Metal Substrates by Chloride Intercalation.
No full textAtomically precise graphene nanoribbons (GNRs) have a wide range of electronic properties that depend sensitively on their chemical structure. Several types of GNRs have been synthesized on metal surfaces through selective surface-catalyzed reactions. The resulting GNRs are adsorbed on the metal surface, which may lead to hybridization between the GNR orbitals and those of the substrate. This makes investigation of the intrinsic electronic properties of GNRs more difficult and also rules out capacitive gating. Here, we demonstrate the formation of a dielectric gold chloride adlayer that can intercalate underneath GNRs on the Au(111) surface. The intercalated gold chloride adlayer electronically decouples the GNRs from the metal and leads to a substantial hole-doping of the GNRs. Our results introduce an easily accessible tool in the in situ characterization of GNRs grown on Au(111) that allows for exploration of their electronic properties in a heavily hole-doped regime
Rare histologic transformation of a CTNNB1 (β-catenin) mutated prostate cancer with aggressive clinical course.
Get PDFBACKGROUND
Catenin (Cadherin-Associated Protein), Beta 1 (CTNNB1) genomic alterations are rare in prostate cancer (PCa). Gain-of-function mutations lead to overexpression of β-catenin, with consequent hyperactivation of the Wnt/β-catenin signaling pathway, implicated in PCa progression and treatment resistance. To date, successful targeted treatment options for Wnt/β-catenin - driven PCa are lacking.
METHODS
We report a rare histologic transformation of a CTNNB1 (β-catenin) mutated metastatic castration resistant prostate cancer (mCRPC), clinically characterized by highly aggressive disease course. We histologically and molecularly characterized the liver metastatic tumor samples, as well as successfully generated patient-derived organoids (PDOs) and patient-derived xenograft (PDX) from a liver metastasis. We used the generated cell models for further molecular characterization and drug response assays.
RESULTS
Immunohistochemistry of liver metastatic biopsies and PDX tumor showed lack of expression of typical PCa (e.g., AR, PSA, PSAP, ERG) or neuroendocrine markers (synaptophysin), compatible with double-negative CRPC, but was positive for nuclear β-catenin expression, keratin 7 and 34βE12. ERG rearrangement was confirmed by fluorescent in situ hybridization (FISH). Drug response assays confirmed, in line with the clinical disease course, lack of sensitivity to common drugs used in mCRPC (e.g., enzalutamide, docetaxel). The casein kinase 1 (CK1) inhibitor IC261 and the tankyrase 1/2 inhibitor G700-LK showed modest activity. Moreover, despite harbouring a CTNNB1 mutation, PDOs were largely insensitive to SMARCA2/4- targeting PROTAC degraders and inhibitor.
CONCLUSIONS
The reported CTNNB1-mutated mCRPC case highlights the potential challenges of double-negative CRPC diagnosis and underlines the relevance of further translational research to enable successful targeted treatment of rare molecular subtypes of mCRPC
Biomechanical evaluation of double-stranded knot configurations in high-strength sutures and tapes.
No full textPURPOSE
Recently, a new dynamic high-strength suture (DC) was introduced, also available in tape form (DT), featuring a salt-infused silicone core attracting water in a fluid environment to preserve tissue approximation. The aims of this study were to (1) assess the influence of securing throw number on knot security of two double-stranded knot configurations (Cow-hitch and Nice-knot) tied with either dynamic (DC and DT) or conventional (FW and ST) high-strength sutures and tapes, and (2) compare the ultimate force and knot slippage of the novel dynamic versus conventional sutures and tapes when used with their minimal number of needed securing throws.
METHODS
Seven specimens of each FW, ST, DC and DT were considered for tying with Cow-hitch or Nice-knots. The base of these Cow-hitch and Nice-knots was secured with surgeons` knots using 1-3 alternating throws. Tensile tests were conducted under physiologic conditions to evaluate knot slippage, ultimate force at rupture, and minimum number of throws ensuring 100% knot security. RESULTS: For both Cow-hitch and Nice-knots, 100% security was achieved with 2 securing throws for DC, DT, ST, and with 3 securing throws for FW. With these minimum numbers of securing throws, ultimate force was significantly higher for Nice-knots versus Cow-hitch tied with DT (p = 0.001) and slippage was significantly less with Nice-knots versus Cow-hitch tied with DC (p = 0.019).
CONCLUSIONS
The minimum number of securing throws required to achieve 100% security was 2 with DC, DT and ST for both Cow-hitch and Nice-knots configurations, in contrast to FW where 3 securing throws were needed. With these minimum numbers of securing throws, Nice-knots were associated with significantly higher ultimate forces when using DT and lower slippage with DC versus Cow-hitch knots
Assessing the clinical utility of ultrasound in general practitioner practices: A systematic review of beneficial and non-beneficial indications : Search strategies
No full textResearch question
The use of ultrasound diagnostic imaging is increasing. Despite the importance of ultrasound, studies indicate that a significant proportion of ultrasound investigations may not significantly impact patient care, meaning the imaging is unlikely to modify patient management or outcomes.
The research question is: What are the indications for ultrasound that demonstrate high clinical value and contribute to patient outcomes, and conversely, what are the indications that lack clinical utility and do not significantly benefit patient care?
To answer the research question of this systematic review project, a systematic literature search was conducted by searching Medline (Ovid), Embase (Ovid), the Cochrane Library, CINAHL (EBSCOhost), and Google Scholar
Sparse 3D Reconstruction via Object-Centric Ray Sampling
No full textWe propose a novel method for 3D object reconstruction from a sparse set of views captured from a 360-degree calibrated camera rig. We represent the object surface through a hybrid model that uses both an MLP-based neural representation and a triangle mesh. A key contribution in our work is a novel object-centric sampling scheme of the neural representation, where rays are shared among all views. This efficiently concentrates and reduces the number of samples used to update the neural model at each iteration. This sampling scheme relies on the mesh representation to ensure also that samples are well-distributed along its normals. The rendering is then performed efficiently by a differentiable renderer. We demonstrate that this sampling scheme results in a more effective training of the neural representation, does not require the additional supervision of segmentation masks, yields state of the art 3D reconstructions, and works with sparse views on the Google’s Scanned Objects, Tank and Temples and MVMC Car datasets. Code available at: https://github.com/llukmancerkezi/ROSTE
Magmatic genesis, hydration, and subduction of the tholeiitic eclogite-facies Allalin gabbro (Western Alps, Switzerland).
Get PDFThe Allalin gabbro of the Zermatt-Saas meta-ophiolite consists of variably metamorphosed Mg- to Fe-Ti-gabbros, troctolites, and anorthosites, which are crosscut by basaltic dykes. Field relationships of the various rock types and petrographic studies together with bulk rock and mineral chemical composition data allow the reconstruction of the complete geological history of the Allalin gabbro. With increasing magmatic differentiation, the incompatible element content in clinopyroxene increases (e.g., REEs and Zr by a factor of 5), whereas the Mg# decreases (from 86.4 to 74.6) as do the compatible element contents (e.g., Cr and Ni by factors of 3.5 and 5, respectively). Exhumation to shallower depths led to subsolidus ductile deformation and cooling of the gabbro followed by the intrusion of fine-grained basaltic dykes, which display chilled margins. Bulk rock data of these dykes reveal strong similarities in fluid-immobile trace element patterns to tholeiitic pillow basalts of the Zermatt-Saas and nearby meta-ophiolites. The recalculated REE patterns of the melt in equilibrium with igneous clinopyroxene is very similar to the REE patterns of the mafic dykes, indicating a cogenetic origin of pillow basalts, dykes, and gabbros. Together with the previously determined Jurassic intrusion age of the gabbro, our observations demonstrate that the Allalin gabbro intruded as a tholeiitic magma in a slow spreading MOR environment of the Piemonte-Ligurian ocean of the Alpine Tethys. Subduction of the Allalin gabbro resulted in different eclogitization extents of the Mg-gabbros as a function of variable hydration degrees. Metagabbros with low extents of hydration record incomplete eclogitization; the magmatic mineralogy (olivine + clinopyroxene + plagioclase) is preserved together with disequilibrium textures in the form of reaction coronae surrounding mineral boundaries. Metagabbros with high extents of hydration are completely eclogitized and display pseudomorphic replacement textures of magmatic minerals by eclogite-facies mineral assemblages, which required significant major to trace element transport across mineral domains. The locally variable extents of hydration took place near the sea floor, as recorded by the presence of Cl-apatite (6.28 wt% Cl), and an increase in B concentrations of minerals pseudomorphically replacing olivine (e.g., chlorite with 0.20-0.31 µg/g B and omphacite with 0.22-0.25 µg/g B) compared to magmatic olivine (0.12-0.16 µg/g B). Moreover, the chemical zonation pattern of metamorphic garnet coronae is different in completely eclogitized gabbros and gabbros with relic igneous minerals, in agreement with a main hydration event prior to subduction. The Allalin gabbro therefore represents a classical example of an oceanic gabbro formed in a slow spreading setting in the mid Jurassic that experienced heterogeneous hydration near the sea floor. Paleogene subduction of the gabbro to 70-80 km depth produced variably equilibrated gabbroic eclogites. In eclogite-facies Mg-gabbros, the water-rich minerals chlorite, talc, and chloritoid pseudomorphing magmatic olivine remained stable to these depths, revealing the potential relevance of hydrated Mg-gabbros as a fluid source at subarc depths in subduction zones.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1186/s00015-024-00461-8
Can large language models predict antimicrobial peptide activity and toxicity?
Get PDFAntimicrobial peptides (AMPs) are naturally occurring or designed peptides up to a few tens of amino acids which may help address the antimicrobial resistance crisis. However, their clinical development is limited by toxicity to human cells, a parameter which is very difficult to control. Given the similarity between peptide sequences and words, large language models (LLMs) might be able to predict AMP activity and toxicity. To test this hypothesis, we fine-tuned LLMs using data from the Database of Antimicrobial Activity and Structure of Peptides (DBAASP). GPT-3 performed well but not reproducibly for activity prediction and hemolysis, taken as a proxy for toxicity. The later GPT-3.5 performed more poorly and was surpassed by recurrent neural networks (RNN) trained on sequence-activity data or support vector machines (SVM) trained on MAP4C molecular fingerprint-activity data. These simpler models are therefore recommended, although the rapid evolution of LLMs warrants future re-evaluation of their prediction abilities
Indication for spinal sensitization in chronic low back pain: mechanical hyperalgesia adjacent to but not within the most painful body area.
Get PDFINTRODUCTION
In 85% of patients with chronic low back pain (CLBP), no specific pathoanatomical cause can be identified. Besides primary peripheral drivers within the lower back, spinal or supraspinal sensitization processes might contribute to the patients' pain.
OBJECTIVES
The present study conceptualized the most painful area (MP) of patients with nonspecific CLBP as primarily affected area and assessed signs of peripheral, spinal, and supraspinal sensitization using quantitative sensory testing (QST) in MP, a pain-free area adjacent to MP (AD), and a remote, pain-free control area (CON).
METHODS
Fifty-nine patients with CLBP (51 years, SD = 16.6, 22 female patients) and 35 pain-free control participants individually matched for age, sex, and testing areas (49 years, SD = 17.5, 19 female participants) underwent a full QST protocol in MP and a reduced QST protocol assessing sensory gain in AD and CON. Quantitative sensory testing measures, except paradoxical heat sensations and dynamic mechanical allodynia (DMA), were Z-transformed to the matched control participants and tested for significance using Z-tests (α = 0.001). Paradoxical heat sensations and DMA occurrence were compared between cohorts using Fisher's exact tests (α = 0.05). The same analyses were performed with a high-pain and a low-pain CLBP subsample (50% quantile).
RESULTS
Patients showed cold and vibration hypoesthesia in MP (all Ps < 0.001) and mechanical hyperalgesia (P < 0.001) and more frequent DMA (P = 0.044) in AD. The results were mainly driven by the high-pain CLBP subsample. In CON, no sensory alterations were observed.
CONCLUSION
Mechanical hyperalgesia and DMA adjacent to but not within MP, the supposedly primarily affected area, might reflect secondary hyperalgesia originating from spinal sensitization in patients with CLBP
Neonatal cerebral ultrasound: anatomical variants and age-related diseases.
Get PDFCerebral ultrasound is a non-invasive imaging technique widely used for the assessment of brain anatomy and diseases in neonates and infants. Indeed, it allows a precise characterization of common variants such as cavum septum pellucidum or diseases like intraventricular hemorrhage. The aim of this pictorial review is to provide a comprehensive overview of the main ultrasound features of the most common cerebral anatomical variants and disorders detectable by cerebral ultrasound using an age-related approach which could support non-subspecialized radiologists
Clinical results of two different three-dimensional plate types for the treatment of mandibular angle fractures: a retrospective analysis.
No full textOBJECTIVES
The purpose of this study was to compare two different designs of three-dimensional osteosynthesis plates for their suitability in the treatment of mandibular angle fractures in terms of sufficient fracture healing and concomitant complications.
MATERIALS AND METHODS
Retrospectively a total of 54 patients with 56 mandibular angle fractures were evaluated. Two different types of three-dimensional plates from the Medartis Trilock system were analyzed: (A) Square design plate (☐-plate) with a thickness of 1.0 mm, and (B) triangular-shaped 3D-plate (△-plate) with a thickness of 1.3 mm. Patient demographics, fracture mechanism and intraoperative details were recorded during an average follow-up period of 1 year.
RESULTS
The utilization of △-plates was observed to entail a considerably lengthier surgical time in contrast to ☐-plate systems (P = 0.037). The application of △-plate showed a tendency of higher incidence of major complications than ☐-plate (P = 0.06), as evidenced by the occurrence of non-union in 2 out of 22 cases, resulting in higher surgical revision rate for △-plate (P = 0.027).
CONCLUSION
Sufficient treatment of mandibular angle fractures is feasible by using 1.0 mm thick, square shaped three-dimensional plate systems. The use of thicker three-dimensional osteosynthesis plates seems to significantly increase the operating time and complication rates, whereby the geometry of the plate seems to have an influence.
CLINICAL RELEVANCE
The plate design could have an impact on treatment outcomes of mandibular angle fractures.
TRIAL REGISTRATION NUMBER
Not applicable
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