Chelating and Bridging Roles of 2-(2-Pyridyl)benzimidazole and Bis(diphenylphosphino)acetylene in Stabilizing a Cyclic Tetranuclear Platinum(II) Complex.

The reaction of complex [Pt(Me)(DMSO)(pbz)], 1, (pbz = 2-(2-pyridyl)benzimidazolate) with [PtMe(Cl)(DMSO)2], B, followed by addition of bis(diphenylphosphino)acetylene (dppac), gave the novel tetranuclear platinum complex [Pt4Me4(μ-dppac)2(pbz)2Cl2], 2, bearing both the pbz and dppac ligands. In this structure, the pbz ligands are both chelating and bridging to stabilize the tetraplatinum framework. The tetranuclear Pt(II) complex was fully characterized by NMR spectroscopy, X-ray crystallography, and mass spectrometry, and its electronic structure was investigated and supported by DFT calculations

Influence of Ancillary Ligands on Photophysical Properties of Cyclometalated Organoplatinum(II) Complexes

Three series of cyclometalated organoplatinum(ii) complexes [Pt(p-MeC6H4)(bhq)(L)], in which bhq is benzo[h]quinolinate and L is PPh3 (1a), PPh2Me (1b), or PPhMe2 (1c); [Pt(p-XC6H4)(bhq)(PPh2Me)], in which X is H (2a), F (2b), Bu-t (2c), OMe (2d), or Me (2e = 1b); and [Pt(bhq)X(PPh2Me)], in which X is CF3CO2 (3a), Cl (3b), or I (3c) were synthesized and fully characterized using multinuclear (H-1 and P-31) NMR spectroscopy and elemental analysis. Typical complexes [Pt(p-MeC6H4)(bhq)(PPhMe2)], 1c, [Pt(p-MeC6H4)(bhq)(PPh2Me)], 2e, and [Pt(bhq)Cl(PPh2Me)], 3b, were further characterized by single crystal X-ray crystallography. The photophysical properties of all the complexes were studied and the influence of changing the ancillary ligands and substituents on their luminescence properties were investigated and the assignments were confirmed by TD-DFT calculations

Phosphorescent heterobimetallic complexes involving platinum(IV) and rhenium(VII) centers, connected by unsupported μ-oxido bridge

Heterobimetallic compounds [(CN)LMe2Pt(mu-O)ReO3] (CN = ppy, L = PPh3, 2a; CN = ppy, L = PMePh2, 2b; CN = bhq, L = PPh3, 2c; CN = bhq, L = PMePh2, 2d) containing a discrete unsupported Pt(IV)-O-Re(VII) bridge have been synthesized through a targeted synthesis route. The compounds have been prepared by a single-pot synthesis in which the Pt(IV) precursor [PtMe2I(CN)L] complexes are allowed to react easily with AgReO4 in which the iodide ligand of the starting Pt(IV) complex is replaced by an ReO4- anion. In these Pt-O-Re complexes, the Pt(IV) centers have an octahedral geometry, completed by a cyclometalated bidentate ligand (CN), two methyl groups and a phosphine ligand, while the Re(VII) centers have a tetrahedral geometry. Elemental analysis, single crystal X-ray diffraction analysis and multinuclear NMR spectroscopy are used to establish their identities. The new complexes exhibit phosphorescence emission in the solid and solution states at 298 and 77 K, which is an uncommon property of platinum complexes with an oxidation state of +4. According to DFT calculations, we found that this emission behavior in the new complexes originates from ligand centered (LC)-L-3 (CN) character with a slight amount of metal to ligand charge transfer ((MLCT)-M-3). The solid-state emission data of the corresponding cycloplatinated(IV) precursor complexes [PtMe2I(CN)L], 1a-1d, pointed out that the replacement of I- by an ReO4- anion helps enhancing the emission efficiency besides shifting the emission wavelengths

Clinical outcome and prognostic factors for central neurocytoma: twenty year institutional experience

Central neurocytomas are uncommon intraventricular neoplasms whose optimal management remains controversial due to their rarity. We assessed outcomes for a historical cohort of neurocytoma patients and evaluated effects of tumor atypia, size, resection extent, and adjuvant radiotherapy. Progression-free survival (PFS) was measured by Kaplan-Meier and Cox proportional hazards methods. A total of 28 patients (15 males, 13 females) were treated between 1995 and 2014, with a median age at diagnosis of 26 years (range 5-61). Median follow-up was 62.2 months and 3 patients were lost to follow-up postoperatively. Thirteen patients experienced recurrent/progressive disease and 2-year PFS was 75% (95% CI 53-88%). Two-year PFS was 48% for MIB-1 labeling >4% versus 90% for ≤4% (HR 5.4, CI 2.2-27.8, p = 0.0026). Nine patients (32%) had gross total resections (GTR) and 19 (68%) had subtotal resections (STR). PFS for >80% resection was 83 versus 67% for ≤80% resection (HR 0.67, CI 0.23-2.0, p = 0.47). Three STR patients (16%) received adjuvant radiation which significantly improved overall PFS (p = 0.049). Estimated 5-year PFS was 67% for STR with radiotherapy versus 53% for STR without radiotherapy. Salvage therapy regimens were diverse and resulted in stable disease for 54% of patients and additional progression for 38 %. Two patients with neuropathology-confirmed atypical neurocytomas died at 4.3 and 113.4 months after initial surgery. For central neurocytomas, MIB-1 labeling index >4% is predictive of poorer outcome and our data suggest that adjuvant radiotherapy after STR may improve PFS. Most patients requiring salvage therapy will be stabilized and multiple modalities can be effectively utilized

Radio-Pathomic Approaches in Pediatric Neurooncology: Opportunities and Challenges

With medical software platforms moving to cloud environments with scalable storage and computing, the translation of predictive artificial intelligence (AI) models to aid in clinical decision-making and facilitate personalized medicine for cancer patients is becoming a reality. Medical imaging, namely radiologic and histologic images, has immense analytical potential in neuro-oncology, and models utilizing integrated radiomic and pathomic data may yield a synergistic effect and provide a new modality for precision medicine. At the same time, the ability to harness multi-modal data is met with challenges in aggregating data across medical departments and institutions, as well as significant complexity in modeling the phenotypic and genotypic heterogeneity of pediatric brain tumors. In this paper, we review recent pathomic and integrated pathomic, radiomic, and genomic studies with clinical applications. We discuss current challenges limiting translational research on pediatric brain tumors and outline technical and analytical solutions. Overall, we propose that to empower the potential residing in radio-pathomics, systemic changes in cross-discipline data management and end-to-end software platforms to handle multi-modal data sets are needed, in addition to embracing modern AI-powered approaches. These changes can improve the performance of predictive models, and ultimately the ability to advance brain cancer treatments and patient outcomes through the development of such models

Online medical crowdfunding in the United States: a cross-sectional analysis of gendered cancer campaign outcomes

This cross-sectional analysis examined online US crowdfunding campaigns from 2010–2018. Campaigns including prostate, breast, bladder, kidney, cervical, uterine, ovarian, testicular, oral, and thyroid cancers were included. Multivariable modeling was utilized to examine predictive factors for successful campaigns. A total of 1830 online cancer campaigns were included in the final analysis. Breast cancer was estimated to be the most frequent online campaign type (n = 3682), followed by cervical (n = 492), kidney (n = 475), ovarian (n = 460), and prostate cancers (n = 382). Breast cancer campaigns generated the most total funding ($15.3 million). In adjusted models, breast cancers generated significantly more donations per campaign than any other cancer. There was no difference in the average amount of funds raised per campaign by most cancer types, except for thyroid (19.4% less than breast, p < 0.001). Friend-authored campaigns generated more funding than self- and family-authored. Male cancers are under-represented, and breast cancer campaigns are disproportionately over-represented in online medical crowdfunding and generate more donations than many other cancers. Gendered differences in cancer crowdfunding are likely multifactorial and may be influenced by social networks and public health campaigns

SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation

SNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects. Nine hypomorphic SNUPN biallelic variants, predominantly clustered in the last coding exon, are ascertained to segregate with the disease. We demonstrate that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts and CRISPR/Cas9-mediated mutant cell lines. Additionally, mutant nuclei exhibit defective spliceosomal maturation and breakdown of Cajal bodies. Transcriptome analyses reveal splicing and mRNA expression dysregulation, particularly in sarcolemmal components, causing disruption of cytoskeletal organization in mutant cells and patient muscle tissues. Our findings establish SNUPN deficiency as the genetic etiology of a previously unrecognized subtype of muscular dystrophy and provide robust evidence of the role of SPN1 for muscle homeostasis

A systematic review and meta-analysis to determine the contribution of mr imaging to the diagnosis of foetal brain abnormalities In Utero.

OBJECTIVES: This systematic review was undertaken to define the diagnostic performance of in utero MR (iuMR) imaging when attempting to confirm, exclude or provide additional information compared with the information provided by prenatal ultrasound scans (USS) when there is a suspicion of foetal brain abnormality. METHODS: Electronic databases were searched as well as relevant journals and conference proceedings. Reference lists of applicable studies were also explored. Data extraction was conducted by two reviewers independently to identify relevant studies for inclusion in the review. Inclusion criteria were original research that reported the findings of prenatal USS and iuMR imaging and findings in terms of accuracy as judged by an outcome reference diagnosis for foetal brain abnormalities. RESULTS: 34 studies met the inclusion criteria which allowed diagnostic accuracy to be calculated in 959 cases, all of which had an outcome reference diagnosis determined by postnatal imaging, surgery or autopsy. iuMR imaging gave the correct diagnosis in 91 % which was an increase of 16 % above that achieved by USS alone. CONCLUSION: iuMR imaging makes a significant contribution to the diagnosis of foetal brain abnormalities, increasing the diagnostic accuracy achievable by USS alone. KEY POINTS: • Ultrasound is the primary modality for monitoring foetal brain development during pregnancy • iuMRI used together with ultrasound is more accurate for detecting foetal brain abnormalities • iuMR imaging is most helpful for detecting midline brain abnormalities • The moderate heterogeneity of reviewed studies may compromise findings

Generating Bessel beams with broad depth-of-field by using phase-only acoustic holograms

[EN] We report zero-th and high-order acoustic Bessel beams with broad depth-of-field generated using acoustic holograms. While the transverse field distribution of Bessel beams generated using traditional passive methods is correctly described by a Bessel function, these methods present a common drawback: the axial distribution of the field is not constant, as required for ideal Bessel beams. In this work, we experimentally, numerically and theoretically report acoustic truncated Bessel beams of flat-intensity along their axis in the ultrasound regime using phase-only holograms. In particular, the beams present a uniform field distribution showing an elongated focal length of about 40 wavelengths, while the transverse width of the beam remains smaller than 0.7 wavelengths. The proposed acoustic holograms were compared with 3D-printed fraxicons, a blazed version of axicons. The performance of both phase-only holograms and fraxicons is studied and we found that both lenses produce Bessel beams in a wide range of frequencies. In addition, high-order Bessel beam were generated. We report first order Bessel beams that show a clear phase dislocation along their axis and a vortex with single topological charge. The proposed method may have potential applications in ultrasonic imaging, biomedical ultrasound and particle manipulation applications using passive lenses.This work was supported by the Spanish Ministry of Economy and Innovation (MINECO) through Project TEC2016-80976-R. NJ and SJ acknowledge financial support from Generalitat Valenciana through grants APOSTD/2017/042, ACIF/2017/045 and GV/2018/11. FC acknowledges financial support from Agencia Valenciana de la Innovacio through grant INNCON00/18/9 and European Regional Development Fund (IDIFEDER/2018/022).Jiménez-Gambín, S.; Jimenez, N.; Benlloch Baviera, JM.; Camarena Femenia, F. (2019). 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